Molecular Mechanisms of Biological Membrane Curvature Generation

When: Wednesday, November 16, 2011 at 4:00 pm
Where: DA 114
Speaker: Dr. Andrey Ivankin
Organization: Illinois Institute of Technology
Sponsor: Biophysics Seminar

Biomembranes undergo extensive shape changes as they perform vital cellular functions.
Instances of controlled membrane curvature include pore formation during virus
entry into cells and killing of bacteria by antimicrobial peptides. Membrane
curvature can be generated by an asymmetric transverse or lateral distribution
of lipids of different molecular shapes within a bilayer, by scaffolding of peripheral
membrane proteins with curved shapes, or by shallow embedding of protein
amphipathic or hydrophobic domains into the lipid matrix. At the same time, the
spatial organization of bilayer constituent molecules, and thus activity of
membrane-bending sequences, can be regulated by membrane curvature. The exact
mechanism of this mechano-chemical interplay governing dynamic remodeling of
cellular membranes remains largely unclear.

Bilayer deformations that a protein produces via embedding its amphipathic or
hydrophobic domains into the lipid matrix are uniquely defined by the depth of
their insertion and the surface area these domains occupy. Shallowly embedded
domains expand mainly the lipid polar heads, while the hydrocarbon chains
remain undisturbed. This leads to a strong asymmetry in spacing between the
tails and headgroups of the membrane lipids and consequently leads to the generation
of a positive membrane curvature. In contrast, when a protein’s domain expands
the polar and hydrocarbon regions of the membrane lipids evenly, only
negligible curvature is produced.

Evidence will be presented that lipids could regulate both membrane penetration depth
and occupied surface area of a protein or a peptide and thus the curvature that
it produces via the insertion mechanism (Fig. 1). Examples of the
lipid-dependent activity of membrane-bending molecules include that of HIV-1
gp41 fusion protein and antimicrobial peptides. Taken together, previous
reports and our data offer a new mechanism of how lipids and proteins could
regulate membrane curvature. Our hypothesis states that lipids may rearrange
locally in response to the protein domains’ binding which then alters the membrane
insertion properties of these domains and curvature they produce.