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Szleifer, Igal

Publications and source records attributed to Szleifer, Igal.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

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↗
DOE OSTI2021

Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function

Extending across multiple length scales, dynamic chromatin structure is linked to transcription through the regulation of genome organization. However, no individual technique can fully elucidate this structure and its relation to molecular function at all length and time scales at both a single-cell level and a population level. Here, we present a multitechnique nanoscale chromatin imaging and analysis (nano-ChIA) platform that consolidates electron tomography of the primary chromatin fiber, optical super-resolution imaging of transcription processes, and label-free nano-sensing of chromatin packing and its dynamics in live cells. Using nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nanometers, sub-megabase genomic size, and an internal fractal structure. The chromatin packing behavior of these domains exhibits a complex bidirectional relationship with active gene transcription. Furthermore, we found that properties of PDs are correlated among progenitor and progeny cells across cell division.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here in this paper, we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Effect of calcium ions on the interactions between surfaces end-grafted with weak polyelectrolytes

We study the interactions between two planar surfaces end-tethered with poly(acrylic acid) polymers in electrolyte solutions containing calcium ions, using a molecular theory. We found that by adding divalent calcium ions to an aqueous solution of monovalent ions leads to a dramatic reduction in the size and range of effective interactions between the two polymer layers. This is caused by the formation of favorable calcium bridges, i.e., complexes of one calcium ion and two carboxylic acid monomers, that reduce the effective charge of the polymer layers and, at sufficient calcium ion concentrations, can cause the polymer layers to collapse. For calcium ion concentrations above approximately 1 mM, the repulsions between the opposing end-grafted surfaces disappear and attractions occur. These attractions are correlated with the occurrence of interlayer divalent calcium bridges and do not occur for poly(acrylic acid) layers in contact with reservoir solutions containing only monovalent ions. This result indicates the suitability of divalent calcium ions to control and change the interaction range and strength, which is a useful property that is desirable in the design of stimuli-responsive nanomaterials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Competitive calcium ion binding to end-tethered weak polyelectrolytes

We have developed a molecular model to describe the structural changes and potential collapse of weak polyelectrolyte layers end-tethered to planar surfaces and spherical nanoparticles as a function of pH and divalent ion concentration.

catalysis (homogeneous), solar (photovoltaic), bio↗
DOE OSTI2017

The effects of chemical fixation on the cellular nanostructure

Chemical fixation is nearly indispensable in the biological sciences, especially in circumstances where cryo-fixation is not applicable. While universally employed for the preservation of cell organization, chemical fixatives often introduce artifacts that can confound identification of true structures. Since biological research is increasingly probing ever-finer details of the cellular architecture, it is critical to understand the nanoscale transformation of the cellular organization due to fixation both systematically and quantitatively. In this work, we employed Partial Wave Spectroscopic (PWS) Microscopy, a nanoscale sensitive and label-free live cell spectroscopic-imaging technique, to analyze the effects of the fixation process through three commonly used fixation protocols for cells in vitro. In each method investigated, we detected dramatic difference in both nuclear and cytoplasmic nanoarchitecture between live and fixed states. But significantly, despite the alterations in cellular nanoscale organizations after chemical fixation, the population differences in chromatin structure (e.g. induced by a specific chemotherapeutic agent) remains. In conclusion, we demonstrated that the nanoscale cellular arrangement observed in fixed cells was fundamentally divorced from that in live cells, thus the quantitative analysis is only meaningful on the population level. This finding highlights the importance of live cell imaging techniques with nanoscale sensitivity or cryo-fixation in the interrogation of cellular structure, to complement more traditional chemical fixation methods. - Highlights: • PWS was employed to monitor fixation process for the same cells in vitro. • Dramatic changes in cellular nanostructure were observed after fixation. • However, the population difference of chromatin structure remains after fixation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Molecular Design of Antifouling Polymer Brushes Using Sequence-Specific Peptoids

Material systems that can be used to flexibly and precisely define the chemical nature and molecular arrangement of a surface would be invaluable for the control of complex biointerfacial interactions. For example, progress in antifouling polymer biointerfaces that prevents nonspecific protein adsorption and cell attachment, which can significantly improve the performance of an array of biomedical and industrial applications, is hampered by a lack of chemical models to identify the molecular features conferring their properties. Poly(N-substituted glycine) “peptoids” are peptidomimetic polymers that can be conveniently synthesized with specific monomer sequences and chain lengths, and are presented as a versatile platform for investigating the molecular design of antifouling polymer brushes. Zwitterionic antifouling polymer brushes have captured significant recent attention, and a targeted library of zwitterionic peptoid brushes with different charge densities, hydration, separations between charged groups, chain lengths, and grafted chain densities, is quantitatively evaluated for their antifouling properties through a range of protein adsorption and cell attachment assays. Specific zwitterionic brush designs are found to give rise to distinct but subtle differences in properties. In conclusion, the results also point to the dominant roles of the grafted chain density and chain length in determining the performance of antifouling polymer brushes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗