Steric confinement of proteins on lipid membranes can drive curvature and tubulation.
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.
Stachowiak
Jeanne C
JC
Sandia National Laboratories, PO Box 969, Livermore, CA 94551, USA. jcstach@sandia.gov
Hayden
Carl C
CC
Sasaki
Darryl Y
DY
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*
D010713:Phosphatidylcholines; D011506:Proteins; D053835:Unilamellar Liposomes; C033223:polyhistidine; C021016:1,2-diphytanoylphosphatidylcholine; D006639:Histidine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
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