Many cellular processes rely on the recognition of cell membranes by peripheral membrane-binding proteins to effect downstream processes such as immune activation or phagocytosis. The lipid composition of these target cell membranes acts as the signal for many of these proteins. However, it is difficult to quantify the sensitivity of these proteins on the lipid composition in a meaningfully comparative way. Depending on the specific system and conditions studied in the literature, equilibrium binding data might be analyzed using different equations such as the Hill equation, Michaelis-Menten equation, or ligand-depletion equation. While the usage of these equations is common, a common set of guidelines dictating their usage for different conditions is lacking. In order to rigorously guide the use of such equations, we have developed a mathematical paradigm relating all of the equilibrium binding equations used in the field to describe the sensitivity of peripheral membrane-binding proteins to lipid composition. From a single "master" equation, we explicitly derive the equations commonly used in the field and, in doing so, make the assumptions underlying their use for different conditions clear and explicit. Here, we present how this mathematical framework has guided our analysis of various lipid-binding modalities that we have encountered in our studies of multiple peripheral membrane-binding proteins.

Mathematical model for the dependence of peripheral membrane binding proteins on lipid composition

ACS Spring 2022

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