title: Decoding information in cell shape.
abstract: 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.
authors.affiliation: Department of Pharmacology and Systems Therapeutics and Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Padmini
authors.initials: P
authors.lastname: Rangamani
authors.forename: Azi
authors.initials: A
authors.lastname: Lipshtat
authors.forename: Evren U
authors.initials: EU
authors.lastname: Azeloglu
authors.forename: Rhodora Cristina
authors.initials: RC
authors.lastname: Calizo
authors.forename: Mufeng
authors.initials: M
authors.lastname: Hu
authors.forename: Saba
authors.initials: S
authors.lastname: Ghassemi
authors.forename: James
authors.initials: J
authors.lastname: Hone
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
authors.forename: Susana R
authors.initials: SR
authors.lastname: Neves
authors.forename: Ravi
authors.initials: R
authors.lastname: Iyengar
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D048430:Cell Shape; D002522:Chlorocebus aethiops; D006801:Humans; D008954:Models, Biological; D051381:Rats; D015398:Signal Transduction
references.citation: Nat Biotechnol. 2002 Apr;20(4):370-5
references.pmid: 11923843
references.citation: Science. 2002 Aug 9;297(5583):1018-23
references.pmid: 12169734
references.citation: Oncogene. 1999 Oct 21;18(43):5936-42
references.pmid: 10557080
references.citation: EMBO J. 2000 Sep 1;19(17):4589-600
references.pmid: 10970852
references.citation: Nat Rev Cancer. 2006 May;6(5):392-401
references.pmid: 16572188
references.citation: Science. 1999 Jan 15;283(5400):381-7
references.pmid: 9888852
references.citation: Biotechnol Prog. 2001 Mar-Apr;17(2):227-39
references.pmid: 11312698
references.citation: Cell Motil Cytoskeleton. 2008 Nov;65(11):841-52
references.pmid: 18677773
references.citation: Nature. 1978 Jun 1;273(5661):345-9
references.pmid: 661946
references.citation: Cell. 2007 Feb 9;128(3):561-75
references.pmid: 17289574
references.citation: J Theor Biol. 2006 Jun 7;240(3):368-73
references.pmid: 16277995
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19264-9
references.pmid: 19033456
references.citation: Mol Cell Biochem. 2007 Jul;301(1-2):241-9
references.pmid: 17294137
references.citation: J Biol Chem. 2007 Jun 29;282(26):19203-16
references.pmid: 17420253
references.citation: Oncogene. 2010 Jan 7;29(1):68-80
references.pmid: 19802012
references.citation: Nat Protoc. 2010 Mar;5(3):491-502
references.pmid: 20203666
references.citation: Biophys J. 2010 May 19;98(10):2136-46
references.pmid: 20483321
references.citation: Curr Biol. 2009 Sep 15;19(17):R762-71
references.pmid: 19906578
references.citation: J Cell Biol. 1992 Jul;118(2):321-33
references.pmid: 1378446
references.citation: Biophys J. 2004 Mar;86(3):1794-806
references.pmid: 14990505
references.citation: J Pharmacol Exp Ther. 2011 Apr;337(1):33-41
references.pmid: 21205920
references.citation: PLoS One. 2011;6(10):e25122
references.pmid: 21984900
references.citation: PLoS One. 2008;3(11):e3735
references.pmid: 19011687
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S323-8
references.pmid: 18955730
references.citation: Science. 2010 Jan 1;327(5961):46-50
references.pmid: 20044567
references.citation: J Biol Chem. 2006 Mar 31;281(13):8917-26
references.pmid: 16418172
references.citation: EMBO Rep. 2010 Sep;11(9):678-84
references.pmid: 20725092
references.citation: Nature. 2005 Dec 1;438(7068):590-6
references.pmid: 16319878
references.citation: Biophys J. 2007 Jul 15;93(2):684-98
references.pmid: 17468161
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14015-20
references.pmid: 16959880
references.citation: Trends Biotechnol. 2001 Oct;19(10):401-6
references.pmid: 11587765
references.citation: Phys Rev Lett. 2004 Sep 3;93(10):108105
references.pmid: 15447457
references.citation: Nat Rev Neurosci. 2007 Feb;8(2):128-40
references.pmid: 17195035
references.citation: J Clin Invest. 2009 Jun;119(6):1417-9
references.pmid: 19487817
references.citation: Biophys J. 2011 Feb 16;100(4):845-57
references.pmid: 21320428
references.citation: PLoS Biol. 2007 Sep;5(9):e233
references.pmid: 17760506
references.citation: Biochem J. 2006 Jul 1;397(1):39-45
references.pmid: 16599904
references.citation: Biochem Soc Trans. 2005 Nov;33(Pt 5):891-5
references.pmid: 16246005
references.citation: Nature. 2009 Feb 26;457(7233):1159-62
references.pmid: 19098897