title: Steric confinement of proteins on lipid membranes can drive curvature and tubulation.
abstract: Deformation of lipid membranes into curved structures such as buds and tubules is essential to many cellular structures including endocytic pits and filopodia. Binding of specific proteins to lipid membranes has been shown to promote membrane bending during endocytosis and transport vesicle formation. Additionally, specific lipid species are found to colocalize with many curved membrane structures, inspiring ongoing exploration of a variety of roles for lipid domains in membrane bending. However, the specific mechanisms by which lipids and proteins collaborate to induce curvature remain unknown. Here we demonstrate a new mechanism for induction and amplification of lipid membrane curvature that relies on steric confinement of protein binding on membrane surfaces. Using giant lipid vesicles that contain domains with high affinity for his-tagged proteins, we show that protein crowding on lipid domain surfaces creates a protein layer that buckles outward, spontaneously bending the domain into stable buds and tubules. In contrast to previously described bending mechanisms relying on local steric interactions between proteins and lipids (i.e. helix insertion into membranes), this mechanism produces tubules whose dimensions are defined by global parameters: domain size and membrane tension. Our results suggest the intriguing possibility that confining structures, such as lipid domains and protein lattices, can amplify membrane bending by concentrating the steric interactions between bound proteins. This observation highlights a fundamental physical mechanism for initiation and control of membrane bending that may help explain how lipids and proteins collaborate to create the highly curved structures observed in vivo.
authors.affiliation: Sandia National Laboratories, PO Box 969, Livermore, CA 94551, USA. jcstach@sandia.gov
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Stachowiak
authors.forename: Carl C
authors.initials: CC
authors.lastname: Hayden
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Sasaki
mesh_terms: D001703:Biophysics; D006639:Histidine / Q000378:metabolism; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000378:metabolism*
chemical_list: D010713:Phosphatidylcholines; D011506:Proteins; D053835:Unilamellar Liposomes; C033223:polyhistidine; C021016:1,2-diphytanoylphosphatidylcholine; D006639:Histidine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
references.citation: Nat Rev Mol Cell Biol. 2007 Mar;8(3):185-94
references.pmid: 17318224
references.citation: Biochemistry. 1990 Jan 9;29(1):76-87
references.pmid: 2322550
references.citation: Nat Cell Biol. 2000 Jan;2(1):42-9
references.pmid: 10620806
references.citation: Nat Cell Biol. 1999 May;1(1):33-9
references.pmid: 10559861
references.citation: Biophys J. 2004 Apr;86(4):2049-57
references.pmid: 15041647
references.citation: J Am Chem Soc. 2009 Jul 1;131(25):8728-9
references.pmid: 19505102
references.citation: Cell. 2005 Aug 26;122(4):605-17
references.pmid: 16122427
references.citation: Phys Rev A. 1991 Dec 15;44(12):8356-8360
references.pmid: 9905991
references.citation: Annu Rev Phys Chem. 2007;58:697-717
references.pmid: 17430092
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13780-4
references.pmid: 19667177
references.citation: Biophys J. 2004 Feb;86(2):905-12
references.pmid: 14747326
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9407-11
references.pmid: 7568142
references.citation: Biochim Biophys Acta. 2009 Jan;1788(1):53-63
references.pmid: 18930706
references.citation: Biophys J. 2005 Jan;88(1):317-33
references.pmid: 15501937
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6775-80
references.pmid: 10359788
references.citation: Langmuir. 2006 May 23;22(11):5095-9
references.pmid: 16700599
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3165-70
references.pmid: 17360623
references.citation: Curr Opin Cell Biol. 2001 Aug;13(4):478-84
references.pmid: 11454455
references.citation: Nat Biotechnol. 2004 Dec;22(12):1567-72
references.pmid: 15558047
references.citation: Biochim Biophys Acta. 2005 Mar 1;1668(2):158-63
references.pmid: 15737326
references.citation: Phys Rev Lett. 2002 Jun 10;88(23):238101
references.pmid: 12059401
references.citation: Phys Rev Lett. 1990 Apr 23;64(17):2094-2097
references.pmid: 10041575
references.citation: FEBS Lett. 2007 May 22;581(11):2098-104
references.pmid: 17382322
references.citation: Nature. 2002 Sep 26;419(6905):361-6
references.pmid: 12353027
references.citation: Nature. 2005 Dec 1;438(7068):590-6
references.pmid: 16319878
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12867-72
references.pmid: 8917511
references.citation: Nature. 1997 Jun 5;387(6633):569-72
references.pmid: 9177342