Role of membrane lipids in leukocyte adhesion

Cambi, A.

Cell membrane lipid composition is prone to modulation during diseases such as cancer, or by pathogens, thereby shaping cell function by altering the adhesive properties of immune cells and cancer cells. How these alterations affect the function of adhesive receptors such as integrin is poorly understood.

Alessandra Cambi's group, Dept. of Cell Biology, theme Nanomedicine in collaboration with physicists of the Institute of Photonic Sciences (Barcelona, Spain) investigated whether and how changes in the lipid nanoenvironment affect nanoscale organization, dynamics and function of the leukocyte-specific integrin LFA-1, which mediates leukocyte transendothelial migration. By combining biochemical assays and single molecule dynamic imaging approaches, Christina Eich (photo below), former PhD student in the Cambi group and currently postdoc at ErasmusMC, demonstrated that generation of ceramide by activation of sphingomyelinase impaired LFA-1-mediated adhesion. This occurs through reduction of LFA-1 lateral mobility, which can be explained by increased immobilization of LFA-1 by coupling to the actin cytoskeleton, and subsequent impaired adhesion. Changes in membrane lipid composition likely affect many other membrane associated receptors, not only integrins, representing an additional level of regulation of receptor function that requires additional research.

This study was recently published in Scientific Reports, top 5 journal in the category Multidisciplinary science and top 2 open-access journal.

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