UC San Diego

The stochastic nature of many fundamental cellular mechanisms such as adhesion, the development of traction forces, and of molecular transport is quite different than typical deterministic structures. Biological structures are truly stochastic in their basic function even when subjected to purely deterministic applied loading. Herein are discussed two areas of vital biological cellular processes, viz. 1) adhesion and the development of traction force and 2) molecular transport Cell adhesion is important for cells to sense and react to the environments. The process of force development along the adhesome within cell focal adhesions is specifically considered. A holistic analysis is presented that explicitly includes the role of a major set of force-bearing proteins involved in force transmission along a "model adhesome" and that leads to the development of traction stress. Our analysis provides a rational description for the various levels of traction stresses that have been reported and of the effect of substrate stiffness. Our approach has the advantage of being quite clear as to how each constituent contributes to the net development of force and traction stress. Nascent adhesions are general precursor to the formation of focal adhesions. Nascent adhesions form when cells come into contact with substrates at all rigidities and generally involve the clustering of ligated integrins that may recruit un-ligated integrins. The flexible, adaptable model we present provides a clear explanation of how these conserved cluster features come about. Our model is based on the interaction among ligated and un-ligated integrins that arise due to deformations that are induced in the cell membrane-cell glycocalyx and substrate system due to integrin activation and ligation. Our simulations reveal effects of various key parameters related to integrin activation and ligation as well as some unexpected and previously unappreciated effects of parameters including integrin mobility and substrate rigidity. To study the significance of advection in the transport of solutes, or particles, within thin biological gaps(channels), we theoretically examine the process driven by stochastic fluid flow caused by random thermal structural motion and compare it with transport via diffusion. The model geometry chosen resembles the synaptic cleft. Our model analysis thus provides unambiguous insight into the prospect of competition of advection vs. diffusion within biological gap-like structures. The importance of the random, versus a regular, nature of structural motion and of the resulting transient nature of advection under random motion are made clear in our analysis.