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Prof Alessandra Cambi

Radboud UMC

Mech(n)anobiology of dendritic cells

Within tissues, cells are subjected to various mechanical forces, including spatial constraints, fluid shear stress and topological cues, each of which contributes to tissue shaping, development and maintenance. How cells interact with and respond to these forces is largely dictated by physical properties of the cells themselves, their neighboring cells and the extracellular matrix (ECM). The process by which cells integrate mechanical stimuli to subsequently translate them into biochemical response is termed mechanotransduction. Tissue stiffness alteration, resulting in disrupted homeostasis of mechanical forces, is involved in many pathologies including pulmonary fibrosis, atherosclerosis and cancer. Despite the importance of mechanotransduction, still little is known about how mechanical forces between cells and their microenvironment contribute to the regulation of tissue organization and function. Specialized leukocytes called dendritic cells (DCs) are key regulators of immune responses. They crawl within tissues patrolling for pathogens or aberrant cells. Upon danger recognition, DCs mature and migrate to lymph nodes to initiate immune responses. During their life-cycle, DCs experience multiple, elastically diverse microenvironments as well as different mechanical stimuli, such as fluid shear variation and cell stretching. This lecture will present bioimaging-driven novel insights into fundamental biophysical mechanisms regulating DC mechanobiology.