TY - JOUR
T1 - XDecoding Information in Cell Shape
AU - Rangamani, Padmini
AU - Lipshtat, Azi
AU - Azeloglu, Evren U.
AU - Calizo, Rhodora Cristina
AU - Hu, Mufeng
AU - Ghassemi, Saba
AU - Hone, James
AU - Scarlata, Suzanne
AU - Neves, Susana R.
AU - Iyengar, Ravi
N1 - Funding Information:
We thank Robert Blitzer, Marc Birtwistle, and the anonymous reviewers for very useful comments on the manuscript. We also thank T. Raymond Solano and Rumana Huq for their technical assistance. Primary cardiac fibroblasts were a kind gift from Dr. Kevin D. Costa; EGFR-eGFP was a kind gift from Linda Pike. This work was supported by NIH Grant (GM-072853 to R.I. and S.S.) and Systems Biology Center Grant (GM-071558). E.U.A. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. Confocal laser scanning microscopy was performed at the MSSM Microscopy Shared Resource Facility, supported with funding from NIH-NCI shared resources (5R24 CA095823-04), NSF Major Research Instrumentation (DBI-9724504), and NIH shared instrumentation (1 S10 RR0 9145-01) grants. Virtual Cell is supported by NIH grant P41-GM103313 from NIGMS. P.R. was supported by a fellowship from training grant (DK007645) from NIDDK.
PY - 2013/9/12
Y1 - 2013/9/12
N2 - Shape is an indicator of cell health. But how is the information in shape decoded? We hypothesize that decoding occurs by modulation of signaling through changes in plasma membrane curvature. Using analytical approaches and numerical simulations, we studied how elongation of cell shape affects plasma membrane signaling. Mathematical analyses reveal transient accumulation of activated receptors at regions of higher curvature with increasing cell eccentricity. This distribution of activated receptors is periodic, following the Mathieu function, and it arises from local imbalance between reaction and diffusion of soluble ligands and receptors in the plane of the membrane. Numerical simulations show that transient microdomains of activated receptors amplify signals to downstream protein kinases. For growth factor receptor pathways, increasing cell eccentricity elevates the levels of activated cytoplasmic Src and nuclear MAPK1,2. These predictions were experimentally validated by changing cellular eccentricity, showing that shape is a locus of retrievable information storage in cells.
AB - Shape is an indicator of cell health. But how is the information in shape decoded? We hypothesize that decoding occurs by modulation of signaling through changes in plasma membrane curvature. Using analytical approaches and numerical simulations, we studied how elongation of cell shape affects plasma membrane signaling. Mathematical analyses reveal transient accumulation of activated receptors at regions of higher curvature with increasing cell eccentricity. This distribution of activated receptors is periodic, following the Mathieu function, and it arises from local imbalance between reaction and diffusion of soluble ligands and receptors in the plane of the membrane. Numerical simulations show that transient microdomains of activated receptors amplify signals to downstream protein kinases. For growth factor receptor pathways, increasing cell eccentricity elevates the levels of activated cytoplasmic Src and nuclear MAPK1,2. These predictions were experimentally validated by changing cellular eccentricity, showing that shape is a locus of retrievable information storage in cells.
UR - http://www.scopus.com/inward/record.url?scp=84884265362&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2013.08.026
DO - 10.1016/j.cell.2013.08.026
M3 - Article
C2 - 24034255
AN - SCOPUS:84884265362
SN - 0092-8674
VL - 154
SP - 1356
JO - Cell
JF - Cell
IS - 6
ER -