Engineering topics

Kosheleva, Irina

Publications and source records attributed to Kosheleva, Irina.

3 records

DOE OSTI2025

Millisecond Phase Transition Kinetics of Lyotropic Liquid Crystalline Nanoparticles Observed by Time‐Resolved Small Angle X‐ray Solution Scattering

This study investigates the dynamic behavior of lyotropic liquid crystal nanoparticles (LCNPs), which are widely recognized for their applications in drug delivery. By employing nanosecond near‐infrared laser pulse‐induced temperature jump (T‐jump) and time‐resolved X‐ray solution scattering, the structural dynamics of phase transitions in phytantriol‐based cubosomes and hexosomes are revealed. Both cubosome and hexosome LCNPs undergo phase transitions into noncrystalline phases at high temperatures. Their phase transition kinetics, occurring within milliseconds (ms) and involving one intermediate structure, are captured. Additionally, the reverse self‐assembly processes of LCNPs were observed, occurring on the timescale of a few hundred ms. To our knowledge, this is the first observation of LCNP T‐jump induced phase transitions on the ms timescale and their reverse self‐assembly. These findings provide valuable insights into the LCNP phase transition processes, with potential implications for drug delivery applications.

Chemistry↗

DOE OSTI2024

Microsecond dynamics control the HIV-1 Envelope conformation

The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timescale dynamics have not been studied experimentally. Here, we used time-resolved, temperature-jump small-angle x-ray scattering to monitor structural rearrangements in an HIV-1 Env SOSIP ectodomain construct with microsecond precision. In two distinct Env variants, we detected a transition that correlated with known Env structure rearrangements with a time constant in the hundreds of microseconds range. A previously unknown structural transition was also observed, which occurred with a time constant below 10 μs, and involved an order-to-disorder transition in the trimer apex. Using this information, we engineered an Env SOSIP construct that locks the trimer in the prefusion closed state by connecting adjacent protomers via disulfides. Our findings show that the microsecond timescale structural dynamics play an essential role in controlling the Env conformation with impacts on vaccine design.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

BioCARS: Synchrotron facility for probing structural dynamics of biological macromolecules

A major goal in biomedical science is to move beyond static images of proteins and other biological macromolecules to the internal dynamics underlying their function. This level of study is necessary to understand how these molecules work and to engineer new functions and modulators of function. Stemming from a visionary commitment to this problem by Keith Moffat decades ago, a community of structural biologists has now enabled a set of x-ray scattering technologies for observing intramolecular dynamics in biological macromolecules at atomic resolution and over the broad range of timescales over which motions are functionally relevant. Many of these techniques are provided by BioCARS, a cutting-edge synchrotron radiation facility built under Moffat leadership and located at the Advanced Photon Source at Argonne National Laboratory. BioCARS enables experimental studies of molecular dynamics with time resolutions spanning from 100 ps to seconds and provides both time-resolved x-ray crystallography and small- and wide-angle x-ray scattering. Structural changes can be initiated by several methods—UV/Vis pumping with tunable picosecond and nanosecond laser pulses, substrate diffusion, and global perturbations, such as electric field and temperature jumps. Studies of dynamics typically involve subtle perturbations to molecular structures, requiring specialized computational techniques for data processing and interpretation. In this review, we present the challenges in experimental macromolecular dynamics and describe the current state of experimental capabilities at this facility. As Moffat imagined years ago, BioCARS is now positioned to catalyze the scientific community to make fundamental advances in understanding proteins and other complex biological macromolecules.

59 BASIC BIOLOGICAL SCIENCES↗