THE SCHOOL OF MATERIALS SCIENCE AND ENGINEERING

GEORGIA INSTITUTE OF TECHNOLOGY

Under the provisions of the regulations for the degree

DOCTOR OF PHILOSOPHY

on Monday, December 3, 2018

2:00 PM
in UA Whitaker BME 1232

will be held the

DISSERTATION PROPOSAL DEFENSE

for

Sunny Hyea Hwang

"Elucidation of the Coupling Between Mechanical and Biophysical Properties of Biological Membranes"

Committee Members:

Prof. J. C. Gumbart, PHYS

Prof. Karl Jacob, MSE

Prof. Donggang Yao, MSE

Prof. Hamid Garmestani, MSE

Prof. Peter Yunker, PHYS

Abstract:

The cell envelope in Gram-negative bacteria comprises two distinct membranes with a cell wall between them. There has been a growing interest in the mechanical adaptation of this cell envelope to the osmotic pressure (or turgor pressure), which is generated by the difference in the concentration of solutes between the cytoplasm and the external environment. However, it remains unexplored how the cell wall, the inner membrane (IM), and the outer membrane (OM) effectively protect the cell from this pressure by bearing the resulting surface tension, thus preventing the formation of inner membrane bulges, abnormal cell morphology, spheroplasts and cell lysis.In this study, we have used molecular dynamics (MD) simulations combined with experiments to resolve how and to what extent models of the IM, OM, and cell wall respond to changes in surface tension. We calculated the area compressibility modulus of all three components in simulations from tension-area isotherms. Experiments on monolayers mimicking individual leaflets of the IM and OM were also used to characterize their compressibility.While the membranes become softer as they expand, the cell wall exhibits significant strain stiffening at moderate to high tensions. We integrate these results into a model of the cell envelope in which the OM and cell wall share the tension at low turgor pressure (0.3 atm) but the tension in the cell wall dominates at high values ( > 1 atm).

The second part of the proposed research will involve an estimation of small-molecule permeation through membranes, which is of critical importance for the delivery of candidate drugs to an intracellular target. In this study, we consider the membrane deformation energy as the dominant factor in crossing the membrane into cells, as measured by in vitro cell-based experiments. We have investigated 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 have used physics-based methods, namely molecular dynamics simulations combined with the inhomogeneous solubility-diffusion model. The estimated permeabilities from our method are compared with other popular methods such as Parallel Artificial Membrane Permeability Assay (PAMPA) experiment.