Online

Farhangian, Atena

Electrical and Biomedical Engineering

2023

Ph. D.

Around 54.4 million of the US population is suffering from arthritis. It is one of the main contributors to activity limitations and is imposing a great cost on society. The main reason behind the lack of a cure for arthritis is the incomplete understanding of the lubrication of the joint. A critical question is the role of phospholipids, especially their mechanical role in relation to cartilage and other molecules present in synovial fluid. The main type of load a joint like a knee endures is compressive forces. The present work is an effort to better understand the molecular-level interactions of the present phospholipid bilayers in the synovial fluid as a function of hydration under external pressure using computer simulations. The dynamics of lipid bilayers are investigated using Coarse-Grained molecular dynamics. Due to the high diversity of lipids in the synovial fluid, 5 different types of lipids with different head groups and acyl chains as tail groups were modeled. The first part of the research investigated the mechanical behavior of phospholipids that are in the liquid crystalline phase (alpha) at body temperature as a function of hydration levels. It was demonstrated that the water content of lipid bilayer structures significantly affects their behavior (area per lipid, lateral diffusion, radial distribution functions) under pressure in a way that higher hydration levels resulted in structures that showed lower resistance to compressive pressure. A semi-empirical model was also developed. The model predicts the pressure at which the rupture of the lipid bilayer structures occurs for different lipids with different hydration levels as well as the change of the area per lipid during the process of applying compressive pressure. The second part of the work investigated DPPC lipid specifically as a lipid that is in the gel (beta) phase at body temperature. We examined how different concentrations of cholesterol in the system enhance the fluidity of the DPPC bilayer. The mechanical behavior of the DPPC bilayer under compression was studied with and without the presence of cholesterol molecules as well. These behaviors include area per lipid and system dimensions, lateral diffusion, radialdistribution functions and order parameters.