Sunny Hyea Hwang
Physics
GA Tech University
Atlanta, GA

Tuesday, July 17, 2018
10:30 am (CT)
3269 Beckman Institute

Abstract

The membranes of practically all living organisms and many viruses are made of a semipermeable lipid bilayer, which is composed of two layers of fatty acids, often containing many embedded proteins. This bilayer, a self-assembled soft material, can take on a multitude of shapes and sizes depending on its composition and its environment. It is responsible for maintaining the boundary of a cell, distinguishing inside from outside, and for selectively mediating the permeability of molecules across it. Quantifying the diverse functionality of membranes requires elucidating their mechanical properties and how those properties depend on their constituents. The bacterial cell envelope presents an especially complex example of membrane structure. It is a multilayered structure that serves to protect these organisms from their unpredictable and often hostile environment. The cell envelope in Gram- negative bacteria is made of two distinct membranes and a cell wall (covalently connected mesh-like elastic network of sugars and peptides) between them. Although there is growing interest in the mechanical adaptation of this cell envelope to the high turgor pressure emanating from within, how the cell wall, inner membrane (IM), and outer membrane (OM) couple together to provide this adaptation remains unexplored. Therefore, the first part of the proposed research is to determine how much osmotic stress each bacterial membrane can withstand and how that stress is communicated to the cell wall. In this study, we will use molecular dynamics (MD) simulations, which provide molecular-level insight into these complex systems that is difficult to obtain by experimental studies alone. Simulations of individual membranes at different protein concentrations as well as membranes coupled to the cell wall will be carried out. In order to describe the membranes elasticity, we will focus on the low-tension (elastic) regime, which can be exploited to measure the area compressibility modulus and Young’s modulus. The high-tension, non-linear regime will also be studied for the cell wall to test the hypothesis that it will exhibit stress stiffening. The second part of the proposed research will involve an estimation of small- molecule perme- ation through membranes, which is of critical importance for the delivery of candidate drugs to an intracellular target. Passive permeation of drugs through cell membranes is strongly dependent on the molecule’s physico-chemical properties. In this study, we will describe a new approach using the deformation free energy of a lipid bilayer based on the principle of a continuum theory. To gain atomistic insight into the passive permeability process, we will use physics-based methods and MD simulation, combined with the inhomogeneous solubility-diffusion model. The estimated permeability from our method will be compared with other popular methods such as Quantitative Structure-Property Relationship (QSAR) analysis.

Fellowship @ Oak Ridge National Lab, Oak Ridge, TN