title: Extracellular matrix structure and nano-mechanics determine megakaryocyte function.
abstract: Cell interactions with matrices via specific receptors control many functions, with chemistry, physics, and membrane elasticity as fundamental elements of the processes involved. Little is known about how biochemical and biophysical processes integrate to generate force and, ultimately, to regulate hemopoiesis into the bone marrow-matrix environment. To address this hypothesis, in this work we focus on the regulation of MK development by type I collagen. By atomic force microscopy analysis, we demonstrate that the tensile strength of fibrils in type I collagen structure is a fundamental requirement to regulate cytoskeleton contractility of human MKs through the activation of integrin-α2β1-dependent Rho-ROCK pathway and MLC-2 phosphorylation. Most importantly, this mechanism seemed to mediate MK migration, fibronectin assembly, and platelet formation. On the contrary, a decrease in mechanical tension caused by N-acetylation of lysine side chains in type I collagen completely reverted these processes by preventing fibrillogenesis.
authors.affiliation: Department of Biochemistry, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo Foundation, University of Pavia, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malara
authors.forename: Cristian
authors.initials: C
authors.lastname: Gruppi
authors.forename: Isabella
authors.initials: I
authors.lastname: Pallotta
authors.forename: Elise
authors.initials: E
authors.lastname: Spedden
authors.forename: Ruggero
authors.initials: R
authors.lastname: Tenni
authors.forename: Mario
authors.initials: M
authors.lastname: Raspanti
authors.forename: David
authors.initials: D
authors.lastname: Kaplan
authors.forename: Maria Enrica
authors.initials: ME
authors.lastname: Tira
authors.forename: Cristian
authors.initials: C
authors.lastname: Staii
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduini
mesh_terms: D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D013718:Tensile Strength; D034061:Thrombopoiesis
chemical_list: D024042:Collagen Type I; D038982:Integrin alpha2beta1