5az Investigating the Biophysics of Receptor-Mediated Cellular Processes

Kit Yan Chan, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250

Receptor-mediated cellular processes are responsible for a wide range of biological phenomena including cellular adhesion/detachment in immune response, cell migration in response to stimulants, and cancer metastasis. These processes are very important in maintaining normal health and understanding these processes is crucial in combating diseases and infections. However, currently the biophysical mechanisms underlying many of these processes are not well understood. My current research utilizes knowledge on cell mechanics, fluid flow, receptor-ligand binding kinetics, and reactive molecular transport to model and examine complex biological processes.

Cellular Detachment in a Shear Flow

A better understanding of the cellular detachment process is essential in combating numerous life-threatening conditions, such as microbial infections, thrombolysis, biofilm breakup, cancers metastasis, etc. This study investigates numerically the cellular detachment process of a modeled Staphylococcus aureus bacterial cell from a collagen-coated surface in a shear flow. The cell is modeled as an elastic capsule with receptor sites located on the cell membrane surface. The coupled flow field and the cell shape are solved using the Immersed Boundary Method; with the elastic membrane forces obtained using a standard Finite Element technique. The receptor-ligand bonds are described by the Hookean spring model. The imposed shear rates are within a range of physiologic shear rates observed in the vasculature, and a range of receptor densities representing the different bacterial strains and growth phases are used in the simulations. The influences of the strength of the shear field, the receptor density on the cell surface, and the cell deformability on the cellular contact area and subsequent detachment (if any) are presented. In vivo studies have demonstrated that unattached bacterial cells have a lower probability to cause infection than an attached cell; hence, favorable conditions promoting cellular detachment are identified and discussed. Advisors: Dr. Charles Eggleton and Dr. Julia Ross (University of Maryland Baltimore County)

The Influence of Membrane Mechanical Properties on Cellular Deformation in a Shear Flow

The deformation of an elastic capsule in a simple shear flow is simulated using the Immersed Boundary Method. Different elastic membrane models representing strain-softening or strain-hardening materials are used in the simulations. Results show that under small deformation regime, there is no significant difference in deformation for all the membrane models examined. However, simulations show that under the large deformation regime, cells described by different membrane models exhibit significant differences on both the steady cell shape and the time to reach steady state. The total membrane elastic energy is shown to be a combination of the contributions from isotropic extension and uniaxial stretching for a capsule deforming under a shear flow. This is in contrary to the case of dominant contribution from isotropic extension in the elastic membrane energy when the capsule deforms under a pure extensional flow. These results suggest that the shear and dilatational modulus of the membrane can be obtained by performing a set of designed cell deformation experiments under controlled flow conditions. Advisor: Dr. Charles Eggleton (University of Maryland Baltimore County).

The presenter also had past research experience on computational fluid dynamics and mass transport: Pulsatile Blood Flow and Gas Transport across a Microfiber Array (with Dr. James Grotberg, University of Michigan), Surfactant-laden Droplet Spreading on a Solid Surface (with Dr. Ali Borhan, Pennsylvania State University).

My future research will continue to investigate complex cellular processes utilizing knowledge in cell mechanics, fluid flow, and receptor-ligands binding kinetics. In addition, the effects of reactive molecular transport (drug) in altering cellular interactions will also be examined.