title: Engineering de novo membrane-mediated protein-protein communication networks.
abstract: Mechanical properties of biological membranes are known to regulate membrane protein function. Despite this, current models of protein communication typically feature only direct protein-protein or protein-small molecule interactions. Here we show for the first time that, by harnessing nanoscale mechanical energy within biological membranes, it is possible to promote controlled communication between proteins. By coupling lipid-protein modules and matching their response to the mechanical properties of the membrane, we have shown that the action of phospholipase A(2) on acyl-based phospholipids triggers the opening of the mechanosensitive channel, MscL, by generating membrane asymmetry. Our findings confirm that the global physical properties of biological membranes can act as information pathways between proteins, a novel mechanism of membrane-mediated protein-protein communication that has important implications for (i) the underlying structure of signaling pathways, (ii) our understanding of in vivo communication networks, and (iii) the generation of building blocks for artificial protein networks.
authors.affiliation: Institute of Chemical Biology and Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK. k.charalabous@imperial.ac.uk
authors.forename: Kalypso
authors.initials: K
authors.lastname: Charalambous
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Booth
authors.forename: Rudiger
authors.initials: R
authors.lastname: Woscholski
authors.forename: John M
authors.initials: JM
authors.lastname: Seddon
authors.forename: Richard H
authors.initials: RH
authors.lastname: Templer
authors.forename: Robert V
authors.initials: RV
authors.lastname: Law
authors.forename: Laura M C
authors.initials: LM
authors.lastname: Barter
authors.forename: Oscar
authors.initials: O
authors.lastname: Ces
mesh_terms: D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C086596:MscL protein, E coli; D010743:Phospholipids; D054497:Phospholipases A2, Secretory