TY - JOUR
T1 - Physical Plasma Membrane Perturbation Using Subcellular Optogenetics Drives Integrin-Activated Cell Migration
AU - Meshik, Xenia
AU - O'Neill, Patrick R.
AU - Gautam, N.
N1 - Funding Information:
This work was funded by the NIH through NIGMS grants GM069027, GM107370, and GM122577. We thank Vani Kalyanaraman for DNA constructs.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Cells experience physical deformations to the plasma membrane that can modulate cell behaviors like migration. Understanding the molecular basis for how physical cues affect dynamic cellular responses requires new approaches that can physically perturb the plasma membrane with rapid, reversible, subcellular control. Here we present an optogenetic approach based on light-inducible dimerization that alters plasma membrane properties by recruiting cytosolic proteins at high concentrations to a target site. Surprisingly, this polarized accumulation of proteins in a cell induces directional amoeboid migration in the opposite direction. Consistent with known effects of constraining high concentrations of proteins to a membrane in vitro, there is localized curvature and tension decrease in the plasma membrane. Integrin activity, sensitive to mechanical forces, is activated in this region. Localized mechanical activation of integrin with optogenetics allowed simultaneous imaging of the molecular and cellular response, helping uncover a positive feedback loop comprising SFK- and ERK-dependent RhoA activation, actomyosin contractility, rearward membrane flow, and membrane tension decrease underlying this mode of cell migration.
AB - Cells experience physical deformations to the plasma membrane that can modulate cell behaviors like migration. Understanding the molecular basis for how physical cues affect dynamic cellular responses requires new approaches that can physically perturb the plasma membrane with rapid, reversible, subcellular control. Here we present an optogenetic approach based on light-inducible dimerization that alters plasma membrane properties by recruiting cytosolic proteins at high concentrations to a target site. Surprisingly, this polarized accumulation of proteins in a cell induces directional amoeboid migration in the opposite direction. Consistent with known effects of constraining high concentrations of proteins to a membrane in vitro, there is localized curvature and tension decrease in the plasma membrane. Integrin activity, sensitive to mechanical forces, is activated in this region. Localized mechanical activation of integrin with optogenetics allowed simultaneous imaging of the molecular and cellular response, helping uncover a positive feedback loop comprising SFK- and ERK-dependent RhoA activation, actomyosin contractility, rearward membrane flow, and membrane tension decrease underlying this mode of cell migration.
KW - amoeboid migration
KW - integrin
KW - mechanotransduction
KW - membrane tension
KW - optogenetics
UR - http://www.scopus.com/inward/record.url?scp=85062337711&partnerID=8YFLogxK
U2 - 10.1021/acssynbio.8b00356
DO - 10.1021/acssynbio.8b00356
M3 - Article
C2 - 30764607
AN - SCOPUS:85062337711
SN - 2161-5063
VL - 8
SP - 498
EP - 510
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
IS - 3
ER -