Gating of a mechanosensitive channel due to cellular flows

On Shun Pak, Y. N. Young, Gary R. Marple, Shravan Veerapaneni, Howard A. Stone

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9822-9827
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number32
DOIs
StatePublished - Aug 11 2015

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Drug delivery
  • Mechanosensitive channels
  • Nanoparticle delivery
  • Vesicles
  • Viscous flow

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