Non-specific interactions between soluble proteins and lipids induce irreversible changes in the properties of lipid bilayers

Soluble proteins in the extracellular matrix experience a crowded environment. However, most of the biophysical studies performed to date have focused on protein concentrations within the dilute regime (well below the mM range). Here, we systematically studied the interaction of model cell membrane systems (giant unilamellar vesicles and supported lipid bilayers) with soluble globular proteins, bovine serum albumin, hemoglobin and lysozyme at physiologically relevant concentrations. To mimic the extracellular environment more closely, we also used fetal bovine serum as a good representative of a biomimetic protein mixture. We found that regardless of the protein used (and thus of their biological function), the interactions between a model cell membrane and these proteins are determined by their physico-chemical characteristics, mainly their dipolar character (or charged patches). In this paper we discuss the specificity and reversibility of these interactions and their potential implications on the living cells. In particular, we report initial evidence for an additional role of glycolipids in cell membranes: that of reducing the effects of non-specific adsorption of soluble proteins on the cell membrane.