title: Gating of a mechanosensitive channel due to cellular flows.
abstract: A multiscale continuum model is constructed for a mechanosensitive (MS) channel gated by tension in a lipid bilayer membrane under stresses due to fluid flows. We illustrate that for typical physiological conditions vesicle hydrodynamics driven by a fluid flow may render the membrane tension sufficiently large to gate a MS channel open. In particular, we focus on the dynamic opening/closing of a MS channel in a vesicle membrane under a planar shear flow and a pressure-driven flow across a constriction channel. Our modeling and numerical simulation results quantify the critical flow strength or flow channel geometry for intracellular transport through a MS channel. In particular, we determine the percentage of MS channels that are open or closed as a function of the relevant measure of flow strength. The modeling and simulation results imply that for fluid flows that are physiologically relevant and realizable in microfluidic configurations stress-induced intracellular transport across the lipid membrane can be achieved by the gating of reconstituted MS channels, which can be useful for designing drug delivery in medical therapy and understanding complicated mechanotransduction.
authors.affiliation: Department of Mechanical Engineering, Santa Clara University, Santa Clara, CA 95053;
authors.forename: On Shun
authors.initials: OS
authors.lastname: Pak
authors.affiliation: Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ 07102;
authors.forename: Y-N
authors.initials: YN
authors.lastname: Young
authors.affiliation: Department of Mathematics, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Gary R
authors.initials: GR
authors.lastname: Marple
authors.affiliation: Department of Mathematics, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Shravan
authors.initials: S
authors.lastname: Veerapaneni
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 hastone@princeton.edu.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Stone
mesh_terms: D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D012212:Rheology; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers
keywords: drug delivery; mechanosensitive channels; nanoparticle delivery; vesicles; viscous flow