Pericyte mechanics and mechanobiology

Abstract

Pericytes are mural cells of the microvasculature, recognized by their thin processes and protruding cell body. Pericytes wrap around endothelial cells and play a central role in regulating various endothelial functions, including angiogenesis and inflammation. They also serve as a vascular support and regulate blood flow by contraction. Prior reviews have examined pericyte biological functions and biochemical signaling pathways. In this Review, we focus on the role of mechanics and mechanobiology in regulating pericyte function. After an overview of the morphology and structure of pericytes, we describe their interactions with both the basement membrane and endothelial cells. We then turn our attention to biophysical considerations, and describe contractile forces generated by pericytes, mechanical forces exerted on pericytes, and pericyte responses to these forces. Finally, we discuss 2D and 3D engineered in vitro models for studying pericyte mechano-responsiveness and underscore the need for more evolved models that provide improved understanding of pericyte function and dysfunction.

Neutrophil transendothelial migration hotspots – mechanisms and implications

“…Many sorts of pericyte-endothelial cell interactions can be observed: invaginations of the pericyte into the lumen of the vessel, adherens junction-based interactions, gap junction-based interactions and adhesion plaques between the two cell types. More details can be found in a recent review paper by Dessalles and colleagues (Dessalles et al, 2021). These physical interactions consequently influence the ability of neutrophils to migrate into the abluminal layer.…”

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“…There is continuous communication between pericytes and vascular endothelial cells that maintain vessel wall integrity, but also contribute to regulating inflammatory and immune processes (reviewed in Grönloh) [ 15 ]. There are chemical and physical interactions that include pericyte invagination, gap junction-based interactions, adherans junction-based interactions and cell–cell adhesion (reviewed in Dessalles) [ 16 ]. The physical interactions are believed to provide an opening or portal for leukocyte migration and extravagation from the circulation to the peri-vascular space.…”

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“…Gap junctions also provide direct communication between the cytoplasm of both cells facilitating the exchange of ions and molecules ( Cuevas et al, 1984 ). Adhesion plaques anchor pericytes to endothelial cells, while peg-and-socket interdigitations penetrate deeply into the endothelial basement membrane supporting intercellular transmission of mechanical forces ( Dessalles et al, 2021 ). Moreover, the contribution of the pericytes to the vascular basement membrane biochemical composition is considered significant due to the unique location of pericytes embedded in the endothelial basement membrane ( Thomsen et al, 2017 ).…”

“…Moreover, the contribution of the pericytes to the vascular basement membrane biochemical composition is considered significant due to the unique location of pericytes embedded in the endothelial basement membrane ( Thomsen et al, 2017 ). Taken together, pericytes encounter “solid contact stresses” due to their direct physical interactions with the endothelial cell, being subjected to hemodynamic stresses and perivascular water flow/shear stresses ( Dessalles et al, 2021 ). The transmural pressure difference “regulated by pericytes” leads to fluid crossing the vascular wall through endothelial cell-cell junctions and mechanically influencing pericytes and flowing around them.…”