Toward a Membrane-Centric Biology.

With advancements of modern biophysical tools and superresolution imaging, cell biology is entering a new phase of research with technological power fitting for membrane dynamics analyses. However, our current knowledge base of cellular signaling events is mostly built on a network of protein interactions, which is incompatible with the essential roles of membrane activities in those events. The lack of a theoretical platform is rendering biophysical analyses of membrane biology supplementary to the protein-centric paradigm. We hypothesize a framework of signaling events mediated by lipid dynamics and argue that this is the evolutionarily obligatory developmental path of cellular complexity buildup. In this framework, receptors are the late comers, integrating into the pre-existing membrane based signaling events using their lipid interface as the point of entry. We further suggest that the reason for cell surface receptors to remain silent at the resting state is via the suppression effects of their surrounding lipids. The avoidance of such a suppression, via ligand binding or lipid domain disruption, enables the receptors to autonomously integrate themselves into the preexisting networks of signaling cascades.