Diffusion of Lipid and Protein Molecules in Cell Membranes

Khoshnood, Atefeh | 2013

1678 Viewed
  1. Type of Document: Ph.D. Dissertation
  2. Language: English
  3. Document No: 44110 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Jalali, Abbas
  7. Abstract:
  8. Lipid membranes are fundamental constituents of cell membranes and are now used in lap-on-a-chip technology. Membranes in living cells contain a significant fraction of proteins, which undergo lateral random movements due to thermal fluctuations and shear forces imposed by the solvent fluid. Prominent natural and biotechnological systems where membranes are highly sheared include the plasma membrane of endothelial cells, and membranes used in biosensors for high throughput screening of drug candidates, and in water purification devices. In these systems membrane is in direct contact with the mainstream suspension flow, which is driven by pressure gradients. The efficiency and function of these systems depend on the properties of suspension flows, diffusion of lipid and protein molecules, and transverse stability of membrane fluctuations. In this thesis, we use coarse grained molecular dynamics simulations and investigate dynamics of sheared membranes with transmembrane proteins. Using proteins of different lengths, we control the effect of hydrophobic mismatch and measure the viscosity and intermonolayer friction of model membranes. We then study the diffusion of lipid and protein molecules in equilibrium and under shear flow. It is found that the diffusion of lipid molecules is normal in all flow conditions though anisotropies are observed in diffusion coefficients. In equilibrium conditions, the motion of proteins is subdiffusive with an exponent of ³ 0:8 š 0:1. Imposing simple shear flow leads to superdiffusive motion of proteins in the flow direction, with the exponent ³ 1:7. To explain the physical mechanism of the observed anomalous diffusion, we define appropriate distribution functions for the head groups of proteins and lipids, and show that a symmetry breaking between the shear forces of two membrane leaflets forces protein–lipid complexes into membrane voids and yields superdiffusion. We then focus on the flow of suspensions in microfluidic devices and show that Brownian diffusion due to thermal fluctuations can destabilize the distribution of particles and increase the volume fraction near the walls. This phenomenon can dramatically affect the performance of integrated devices that contain membranes as their separatrices. Diffusion and transport of lipids and and proteins generate sustained transverse fluctuations in the membrane and it is important to know whether such fluctuations can become unstable with detectable micron-scale wavelengths. We use the results of molecular dynamics simulations and introduce a continuum model for the dynamics of lipid membranes under shear flow, and carry out a linear stability analysis to calculate critical wavelengths of time-varying membrane oscillations. The influence of intermonolayer friction and membrane viscosity, which are controlled by transmembrane proteins, is studied on the stability of sheared membranes. Our findings can be directly used in the design of stable biosensors and water purification devices
  9. Keywords:
  10. Braodcast ; Biomembranes ; Suspension System ; Lipid Molecules ; Protein Molecules ; Cell Membrane

 Digital Object List