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198 records · Page 11

The Prevalence of Controlled Rest as a Countermeasure to Sleepiness on the Flight Deck

Despite the introduction of flight, duty, and rest time regulations to reduce the risk of sleepiness, airline pilots often encounter elevated sleepiness during flight. To combat this sleepiness, in some instances, pilots can take a short nap on the flight deck (controlled rest) to improve their alertness. Little is known, however, as to when and how often this countermeasure is used operationally.

sleepiness↗

Schedule Factors Associated with the Use of Controlled Rest in a Long-Haul Airline

Controlled Rest (CR) refers to a short, voluntary nap opportunity taken by pilots on the flight deck as a countermeasure to unanticipated sleepiness in flight. This study explores the profile of CR use in a long-haul commercial airline. Forty-four pilots wore actiwatches and filled in an application-based sleep/work diary for approximately 2 weeks. After merging sleep diary, actigraphy, and schedule data, complete records were analyzed from 240 flights. Sleep was estimated during CR intervals using the Philips Actiware 6.0.9 (Bend, OR) software with wake threshold set to medium. Timing of sleep periods and flight schedules were analyzed relative to home-base time. A mixed-effects binary logistics regression was used to analyze the impact of schedule factors on CR. Preliminary analyses revealed that CR was taken on 45% (n=107) of flights. Average sleep duration within these rest periods was estimated as 24.8 ± 16.1 minutes. CR was more frequent on return flights (arriving at home-base; 58%, n=69) vs. outbound flights (departing from home-base, 31%, n=38; p<0.001). There was no difference for direction of travel (eastbound: 49%, n= 56; westbound: 40%, n= 44; northbound/southbound: 50%, n=7; p=0.272). CR was more frequent on 2-pilot flights (62%, n=81) compared to augmented crew flights (24%, n=26; p<0.001). Of note, 21% (n=23) of augmented flights contained both CR and Bunk Rest. CR was more frequent on flights <10h duration (<10h: 59%, n=78; >10h: 27%, n=29; p<0.001). Flights departing between 12:00h-19:59h (25%, n=23; p<0.026) had the lowest frequency of CR. Data from this airline show that CR is most commonly used as a countermeasure to sleepiness on return, unaugmented, <10h duration, and nighttime flights. The direction of travel did not influence the use of CR. Future studies are required to determine generalizability of these results to other airlines.

Hilditch, Cassie↗

Controlled Rest: Profile of Use, Challenges, and Best Practices

Despite the introduction of flight, duty, and rest time regulations to reduce the risk of sleepiness, airline pilots often encounter elevated sleepiness during flight. To combat this sleepiness, in some instances, pilots can take a short nap on the flight deck (controlled rest) to improve their alertness. Little is known, however, as to when and how often this countermeasure is used operationally. Methods: Forty-four pilots from a European carrier wore actiwatches and filled in an electronic sleep and work diary for approximately 2 weeks resulting in data from 239 flights. Self-reported in-flight rest periods were used to set rest intervals and sleep was estimated within these intervals using Philips Actiware 6.0.9. Wake threshold selection was set to medium; sleep threshold detection algorithm was set to 10 immobile minutes at sleep onset and sleep end. Timing of sleep periods was analyzed relative to home base time. Results: Preliminary analyses showed that controlled rest was taken on 46% (n=110) of flights. On 23 flights (10%) pilots reported taking two controlled rest periods. Sleep, as estimated by actigraphy, was achieved during 80% (n=106) of controlled rest periods. The mean sleep duration was 32 (± 12) minutes estimated within successful controlled rest periods. Approximately two-thirds (67.5%, n=81) of all rest periods were initiated during home base time night (0000h-0800h). On 11% (n=26) of flights, pilots also reported taking bunk rest (longer rest period in a designated sleeping facility).Conclusion:This study shows that controlled rest is commonly used as a countermeasure to sleepiness on the flight deck. Further analysis is required to determine what other factors contribute to the decision to take controlled rest, and how effective it is in reducing sleepiness on the flight deck.

Hilditch, Cassie J.↗

Mitigating fatigue on the flight deck: how is controlled rest used in practice?

Controlled Rest (CR) refers to a short, voluntary nap opportunity taken by pilots on the flight deck as a countermeasure to unanticipated sleepiness in flight. This study explores the profile of CR use in a long-haul commercial airline. Forty-four pilots wore actiwatches and filled in an application-based sleep/work diary for approximately 2 weeks resulting in complete records from 239 flights. Timing of sleep periods and flight schedules were analyzed relative to home-base time. Pearson correlations were used to assess the influence of pilot demographics on CR use. A mixed-effects logistic regression was used to analyze the impact of schedule factors on CR. CR was taken on 46% (n=110) of flights, with 80% (n=106/133) of all CR attempts estimated by actigraphy to have successfully achieved sleep. Average sleep duration during successful rest periods was estimated as 31.7 ± 12.2 minutes. CR was more frequent on return (60%, n=71) vs. outbound flights (33%, n=39); 2-pilot (69%, n=83) vs. >2-pilot flights (23%, n=27); <10h (63%, n=80) vs. >10h duration flights (27%, n=30); and night (55%, n=76) vs. day flights (34%, n=34) (all p≤0.001). There was no significant difference for direction of travel (eastbound: 51%, n= 57; westbound: 40%, n= 44; p=0.059). Of note, 22% (n=26) of augmented flights contained both CR and bunk rest. Data from this airline show that CR is most commonly used as a countermeasure to sleepiness on flights <10h duration (2-pilot crews) and home-base nighttime flights. Future studies are required to determine the generalizability of these results to other airlines.

sleepiness↗

Sleep Obtained by Cabin Crewmembers during a Long-haul Flight

Sleep loss and circadian disruption pose a significant risk in safety-sensitive occupations. In aviation, many studies have demonstrated how inflight rest locations influence alertness and performance among pilots, but few studies have evaluated cabin crew. The purpose of the present study was to evaluate sleep outcomes among cabin crewmembers sleeping in a bunk compared to a jump seat during one long-haul route. Thirty-one (6 male) cabin crewmembers (age M = 30, SD = +/-13) flew the same long-haul route (outbound and return) with a flight duration of 10:41 (± 0:14) hours. Participants were randomly assigned to fly on an aircraft with a bunk or a jump seat for their sleep opportunity. Participants wore an Actiwatch (Phillips-Respironics Spectrum) throughout the entire study and completed a sleep diary at bedtime and upon waking. During flight they completed a nap diary entering the start time of the inflight sleep (if any) and the duration. Sixty-five flights (32 outbound and 33 return) were included in the analyses. Seventy-seven percent of the flights had a bunk and 23% had a jump seat. Crewmembers obtained M = 146.46 (± 67.20) minutes of rest out of which they slept M = 125.33 (± 64.91) minutes in the bunk. While using the jump seat, crewmembers obtained M = 169.53 (± 133.30) minutes of rest out of which they slept M = 142.92 (± 149.72) minutes. When crewmembers slept in the bunk, sleep latency was shorter (M = 13.69 ± 12.64 minutes) and efficiency was better (M = 76.16 ± 16.09 %) compared to the jump seat (sleep onset: M = 16.77 ± 13.89 minutes; sleep efficiency: M = 60.64 ± 17.42 %). We found that cabin crewmembers slept for longer time when they used the jump seat. They fell asleep faster and their sleep efficiency was better when using the bunk compared to the jump seat. Further research is needed to understand how sleep quality and subsequent performance are influenced by sleep opportunity in a bunk compared to a jump seat.

cabin crew↗

Sleep Obtained by Cabin Crewmembers during a Long-haul Flight

Sleep loss and circadian disruption pose a significant risk in safety-sensitive occupations. In aviation, many studies have demonstrated how inflight rest locations influence alertness and performance among pilots, but few studies have evaluated cabin crew. The purpose of the present study was to evaluate sleep outcomes among cabin crewmembers sleeping in a bunk compared to a jump seat during one long-haul route. Thirty-one (6 male) cabin crewmembers (age M = 30, SD = +/-13) flew the same long-haul route (outbound and return) with a flight duration of 10:41 (± 0:14) hours. Participants were randomly assigned to fly on an aircraft with a bunk or a jump seat for their sleep opportunity. Participants wore an Actiwatch (Phillips-Respironics Spectrum) throughout the entire study and completed a sleep diary at bedtime and upon waking. During flight they completed a nap diary entering the start time of the inflight sleep (if any) and the duration. Sixty-five flights (32 outbound and 33 return) were included in the analyses. Seventy-seven percent of the flights had a bunk and 23% had a jump seat. Crewmembers obtained M = 146.46 (± 67.20) minutes of rest out of which they slept M = 125.33 (± 64.91) minutes in the bunk. While using the jump seat, crewmembers obtained M = 169.53 (± 133.30) minutes of rest out of which they slept M = 142.92 (± 149.72) minutes. When crewmembers slept in the bunk, sleep latency was shorter (M = 13.69 ± 12.64 minutes) and efficiency was better (M = 76.16 ± 16.09 %) compared to the jump seat (sleep onset: M = 16.77 ± 13.89 minutes; sleep efficiency: M = 60.64 ± 17.42 %). We found that cabin crewmembers slept for longer time when they used the jump seat. They fell asleep faster and their sleep efficiency was better when using the bunk compared to the jump seat. Further research is needed to understand how sleep quality and subsequent performance are influenced by sleep opportunity in a bunk compared to a jump seat.

cabin crewmembers↗

Rise and Shine: Using Light as a Countermeasure to Sleep Inertia

INTRODUCTION: Sleep inertia describes the phenomenon of sleepiness and poor performance experienced after waking from sleep. This period of impaired alertness and performance is of significant concern to workers who nap on shift, or work on-call and are required to perform safety-critical tasks soon after waking (e.g., emergency services, healthcare, military). Light has been shown to acutely improve alertness during sleep deprivation and circadian misalignment. In this study, we assessed the efficacy of blue-enriched light to improve alertness and mood immediately after waking from SWS, i.e., during the sleep inertia period. METHODS: Twelve participants kept a sleep schedule of 8.5 h for 5 nights and 5 h for one night prior to the overnight laboratory visit (confirmed by actigraphy). Participants went to bed at their scheduled habitual bedtime in the laboratory and were monitored by standard polysomnography. After at least 5 min of SWS, participants were awoken and exposed to either red ambient light (control) or blue-enriched light (light) for 1 h. During this time, participants completed a subjective scale of alertness (Karolinska Sleepiness Scale, KSS) and visual analogue scales (VAS) of mood at 2 min, 17 min, 32 min, and 47 min after waking. Following this sleep inertia measurement period, all lights were turned off and participants were allowed to return to sleep. They were then awoken again from their subsequent SWS period and exposed to the opposite condition (control or light). A linear mixed-effects model with fixed effects of condition, time, and condition*time and a random effect of participant was used to determine the impact of light across the testing period. An average of baseline responses (pre-sleep) was included as a covariate. RESULTS: Compared to the control condition, participants exposed to blue-enriched light reported feeling more alert (KSS: F1,77=4.955, p=.029; VASalert: F1,77=8.226, p=.005), more cheerful (VAScheerful: F1,77=8.615, p=.004), less depressed (VASdepressed: F1,77=4.649, p=.034), and less lethargic (VASlethargic: F1,77=5.652, p=.020). DISCUSSION: Exposure to blue-enriched light immediately after waking from SWS may help to improve subjective alertness and mood. Future analyses will explore whether these findings extend to effects on cognitive performance. This countermeasure to sleep inertia may be suitable for implementation to alert crew members during mid-sleep emergencies but requires further testing in field settings.

alertness↗

Controlled Rest: Investigating the Use of an In-Flight Sleepiness Countermeasure

INTRODUCTION: Sleepiness is commonly reported amongst commercial airline pilots and is recognized as a safety risk due to its impact on performance. Controlled Rest (CR) refers to a short, voluntary nap opportunity taken by pilots on the flight deck as a countermeasure to unanticipated sleepiness in flight. This study explores the profile of CR use in a long-haul commercial airline. METHODS: Forty-four pilots filled in an application-based sleep/work diary and wore actiwatches for approximately 2 weeks. Complete data sets from 239 flights including sleep diaries, actigraphy, and schedules were merged and analyzed. Sleep diary entries were used to set CR intervals in the actigraphy software, which was then used to predict sleep within these intervals. All time-stamps of sleep periods and flight schedules were adjusted for home-base time of the pilots. Pearson Correlations were used to assess the influence of pilot demographics on CR use. A mixed-effects logistic regression was used to analyze the impact of schedule factors on CR. RESULTS: Pilots reported taking CR on 46% (n=110) of observed flights. Average CR attempt duration was 43.1 ± 11.0 minutes. Eighty-percent (n=106/133) of all CR attempts were estimated by actigraphy to have successfully achieved sleep with an average sleep duration during successful rest periods of 31.7 ± 12.2 minutes. Captains reported taking CR on 38% of flights (n=39/102), compared to First Officers reporting 52% (n=71/137) of flights with CR (p=0.131). Age, experience, BMI, and sleep need were not associated with the percentage of flights with CR (all p>0.244). The following schedule factors were associated with a higher frequency of CR: night (55%, n=76) vs. day flights (34%, n=34); <10h (63%, n=80) vs. >10h duration flights (27%, n=30); return (60%, n=71) vs. outbound flights (33%, n=39); and 2-pilot (69%, n=83) vs. >2-pilot flights (23%, n=27) (all p≤0.001). There was a trend for more CR on eastbound flights, but this was not significant (eastbound: 51%, n= 57; westbound: 40%, n= 44; p=0.059). Of note, 22% (n=26) of augmented flights (>2-pilots) contained both CR and Bunk Rest (in a designated rest facility). DISCUSSION: Data from this airline show that pilots commonly use CR to mitigate sleepiness in-flight, especially on flights <10h duration and during home-base nighttime flights. Future studies are required to determine generalizability of these results to other airlines.

sleepiness↗

Changes in Alertness and Performance Over Time During Long-Haul Flying Across Multiple Time Zones

BACKGROUND: Long-haul pilots experience high levels of fatigue and circadian disruptions due to long work hours and flying over multiple time zones. The aim of this study was to describe changes in alertness and performance among flight crews during long-haul flights crossing multiple time zones. METHODS: All pilots flying long-haul operations from a single airline were eligible to participate. All participants collected data for ~2 weeks of their normal work schedule within airline operations, with at least two long-haul rotations, including rest days and layovers. Participants wore an Actiwach throughout the entire study period and completed a sleep diary (at bedtime, upon waking up and after each nap). Each participant completed a 5-min Psychomotor Vigilance Task (PVT) and a Karolinska Sleepiness Scale (KSS) pre-flight, on top-of-descent (TOD; inflight) and at the end of each flight (post-flight). Response speed (1/RT x 1000), lapses (RT > 500 ms), and alertness were assessed over time pre-flight, TOD, post-flight, using mixed-effects models with participant as a random factor. Linear models were assumed for response speed and alertness, while a negative binomial distribution was specified for lapses due to overdispersion. RESULTS: Forty-four long-haul pilots participated in the study (5 female; mean age 44.25 ± 10.06 yrs; mean flight hours 9834.3; ± 5334.1 hrs). Lapses increased post-flight relative to pre-flight (F(2, 665) = 3.67, p < 0.05). There was a main effect of response speed (F(2, 665) = 21.45, p < 0.001) with slower speed inflight and postflight compared to preflight (p < 0.001). The KSS increased over time from M = 4.02 (± 1.35) preflight to M = 5.15 (± 1.58) inflight, to M = 6.7 (± 1.51) postflight (F(2, 701) = 182.63, p < 0.001). DISCUSSION: Our preliminary analyses showed that both performance and subjective alertness worsened from the beginning to the end of a flight. Additional analyses will be conducted to investigate the changes in alertness and performance by direction of travel, sleep history, and flight timing and duration.

long-haul↗

Can Pre-Flight Subjective Sleepiness Predict the Use of Controlled Rest on the Flight Deck?

Pilot sleepiness in flight continues to be an issue in aviation due to irregular and extended working hours. In some regions of the world, pilots are allowed to use an in-flight countermeasure called controlled rest, which involves taking a short nap on the flight deck. The use of this countermeasure in practice is understudied. We aimed to investigate whether subjective sleepiness ratings taken pre-flight are predictive of controlled rest use.

aviation↗

Investigating the Causes and Consequences of Controlled Rest on the Flight Deck

INTRODUCTION: Long and irregular working hours can lead to fatigue in aviation operations. In some regions, a short nap taken on the flight deck (known as controlled rest) can be used as a countermeasure to unexpected in-flight sleepiness. We aimed to investigate the impact of taking controlled rest on self-reported sleepiness at top-of-descent. METHODS: Data from 120 long-haul (> 6 h flight duration), unaugmented flights were analyzed (n = 31 pilots). Pilots wore actigraphs and completed sleep logs before and during trips. At pre-flight and top-of-descent, pilots completed a Karolinska Sleepiness Scale (KSS). A mixed-effects model was used to assess the impact of controlled rest on KSS at top-of-descent. Sleep duration in the 48 hours prior to departure, timing of the flight (day vs. night), and pre-flight KSS scores were included as covariates. RESULTS: Due to missing data, complete data from 83 flights (n = 29 participants) were available in the analyses of the KSS. There were no differences by controlled rest status for KSS scores at top-of-descent (estimated marginal means ± SEM with controlled rest: 5.10 ± 0.22, without controlled rest: 5.37 ± 0.29; p = .45, η2p = 0.01). DISCUSSION: Our results suggest that there is no difference in self-reported sleepiness at top-of-descent on flights in which controlled rest was taken compared to flights without controlled rest. Further research is necessary to determine the impact of controlled rest on objective measures of performance at top-of-descent.

aviation↗

Jet Lag, Sleep Timing, and Sleep Inertia

This chapter explores the causes, consequences, and countermeasures of jet lag, mistimed sleep, and sleep inertia. Jet lag can occur when rapidly crossing multiple time zones (e.g., trans-meridian travel for long-haul pilots). The desynchrony between the body’s biological clock, or circadian rhythm, and the new day-night cycle can lead to indigestion, sleep disturbances, fatigue, and cognitive impairments. Mistimed sleep can also occur within a time zone. In the case of night shiftwork, sleep is displaced to the daytime which leads to poor sleep and increased fatigue at night due to the combination of pressures from the two-process model of sleep regulation: sleep loss (homeostatic pressure); and being awake when the body is promoting sleep (circadian pressure). There is also a third process of sleep regulation called sleep inertia, which refers to the brief period of fatigue and impaired cognitive performance experienced after waking. Sleep inertia can be a fatigue risk for transportation workers who work on-call (e.g., emergency services) or who nap on shift (e.g., long-haul truck drivers) and are required to perform a safety-critical task soon after waking. For each of these fatigue risks, strategic exposure to bright light can be used to help realign sleep timing and to promote alertness.

sleep inertia↗

The Impact of Controlled Rest on Neurobehavioral Outcomes at Top-of-Descent

INTRODUCTION: Long and irregular working hours can lead to fatigue in aviation operations. In some regions, a short nap taken on the flight deck (known as controlled rest) can be used as a countermeasure to unexpected in-flight sleepiness. We aimed to investigate the impact of taking controlled rest on neurobehavioral measures at top-of-descent. METHODS: Data from 120 long-haul (> 6 h flight duration), unaugmented flights were analyzed (n = 31 pilots). Pilots wore actigraphs and completed sleep logs before and during trips. At pre-flight and top-of-descent, pilots completed a 5-minute psychomotor vigilance task (PVT) and Karolinska Sleepiness Scale (KSS). A series of mixed-effects models were conducted to assess the impact of controlled rest on outcome measures at top-of-descent. Sleep duration in the prior 48 hours, timing of the flight, and pre-flight scores for each measure were included as covariates. RESULTS: Due to missing data, complete data from 76 flights (n = 28 participants) were available in the models examining the PVT metrics, and data from 83 flights (n = 29 participants) were available in the analyses of the KSS. Pilots who took controlled rest had faster response speeds at top-of-descent (p = .03, η2p = 0.07; estimated marginal mean [EMM] = 4.19, standard error [SE] = 0.07, 95% CI [4.08, 4.29]) than those who did not take controlled rest (EMM = 4.00, SE = 0.05, 95% CI [3.86, 4.14]). There were no differences by controlled rest status for KSS scores and PVT lapses (p values > .05, η2p values ≤ 0.01). DISCUSSION: Our results suggest that taking controlled rest may improve vigilant attention at critical phases of flight and, thus, may be a useful fatigue management tool during unaugmented flights. Further research is necessary to determine the impact of factors on the decision to take controlled rest (e.g., airline culture, personal preference) and how the controlled rest policy is applied in practice.

aviation↗

The Impact of Controlled Rest on Self-Reported Sleepiness at Top-of-Descent

INTRODUCTION: Long and irregular working hours can lead to fatigue in aviation operations. In some regions, a short nap taken on the flight deck (known as controlled rest) can be used as a countermeasure to unexpected in-flight sleepiness. We aimed to investigate the impact of taking controlled rest on self-reported sleepiness at top-of-descent. METHODS: Data from 120 long-haul (> 6 h flight duration), unaugmented flights were analyzed (n = 31 pilots). Pilots wore actigraphs and completed sleep logs before and during trips. At pre-flight and top-of-descent, pilots completed a Karolinska Sleepiness Scale (KSS). A mixed-effects model was used to assess the impact of controlled rest on KSS at top-of-descent. Sleep duration in the 48 hours prior to departure, timing of the flight (day vs. night), and pre-flight KSS scores were included as covariates. RESULTS: Due to missing data, complete data from 83 flights (n = 29 participants) were available in the analyses of the KSS. There were no differences by controlled rest status for KSS scores at top-of-descent (estimated marginal means ± SEM with controlled rest: 5.10 ± 0.22, without controlled rest: 5.37 ± 0.29; p = .45, η2p = 0.01). DISCUSSION: Our results suggest that there is no difference in self-reported sleepiness at top-of-descent on flights in which controlled rest was taken compared to flights without controlled rest. Further research is necessary to determine the impact of controlled rest on objective measures of performance at top-of-descent.

aviation↗

Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine

The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host–microbiome metabolic interactions.

59 BASIC BIOLOGICAL SCIENCES↗

Charge regulation mechanism in end-tethered weak polyampholytes

Weak polyampholytes, containing oppositely charged dissociable groups, are expected to be responsive to changes in ionic conditions. Here, we determine structural and thermodynamic properties, including the charged groups’ degrees of dissociation, of end-tethered weak polyampholyte layers as a function of salt concentration, pH, and the solvent quality. For diblock weak polyampholytes grafted by their acidic blocks, we find that the acidic monomers increase their charge while the basic monomers decrease their charge with decreasing salt concentration for pH values less than the pK a value of both monomers and vice versa when the pH > pK a . This complex charge regulation occurs because the electrostatic attraction between oppositely charged blocks is stronger than the repulsion between monomers with the same charge in both good and poor solvents when the screening by salt ions is weak. This is shown by the retraction of the top block into the bottom layer. In the case of poor solvent conditions to the basic block (the top block), we find lateral segregation of basic monomers into micelles, forming a two-dimensional hexagonal pattern on the surface at intermediate and high pH values for monovalent salt concentrations from 0.01 to 0.1 M. When the solvent is poor to both blocks, we find lateral segregation of the grafted acidic block into lamellae with longitudinal undulations of low and high acidic monomer density. By exploiting weak block polyampholytes, our work expands the parameter space for creating responsive surfaces stable over a wide range of pH and salt concentration.

36 MATERIALS SCIENCE↗

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

Peptide amphiphiles are a class of molecules that can self-assemble into a variety of supramolecular structures, including high-aspect-ratio nanofibers. It is challenging to model and predict the charges in these supramolecular nanofibers because the ionization state of the peptides are not fixed but liable to change due to the acid-base equilibrium that is coupled to the structural organization of the peptide amphiphile molecules. Here, we have developed a theoretical model to describe and predict the amount of charge found on self-assembled peptide amphiphiles as a function of pH and ion concentration. In particular, we computed the amount of charge of peptide amphiphiles nanofibers with the sequence C 16 − V 2 A 2 E 2 . In our theoretical formulation, we consider charge regulation of the carboxylic acid groups, which involves the acid-base chemical equilibrium of the glutamic acid residues and the possibility of ion condensation. The charge regulation is coupled with the local dielectric environment by allowing for a varying dielectric constant that also includes a position-dependent electrostatic solvation energy for the charged species. We find that the charges on the glutamic acid residues of the peptide amphiphile nanofiber are much lower than the same functional group in aqueous solution. There is a strong coupling between the charging via the acid-base equilibrium and the local dielectric environment. Our model predicts a much lower degree of deprotonation for a position-dependent relative dielectric constant compared to a constant dielectric background. Furthermore, the shape and size of the electrostatic potential as well as the counterion distribution are quantitatively and qualitatively different. These results indicate that an accurate model of peptide amphiphile self-assembly must take into account charge regulation of acidic groups through acid–base equilibria and ion condensation, as well as coupling to the local dielectric environment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗