Cell contact with extracellular matrix proteins (ECMs) leads to
activation of specific biochemical signaling pathways and to cyto-skeletal modifications that regulate processes such as cell differentiation,
migration and apoptosis. Mechanical properties of ECMs
play an important role in determining cells behavior during these
processes. In the bone marrow, ECMs concur to the generation
of cues that are important for hemopoietic stem cells maturation
and differentiation. Sites around the endosteal bone and vascular
districts have been proposed as critical niches for stem cell differentiation
into megakaryocytes (Mks).
In this scenario, fibrillar type I collagen seems to be a key regulator
of platelet release, as in vitro adhesion of Mks to this protein
inhibits platelet release through the generation of a bulk cell contraction
mediated by mechano-sensitive proteins, such as fibronectin,
Rho-GTPase and myosin, that lead to cell spreading
overtime.
In this work we have used a chemical modified collagen that
completely override in vitro collagen ligand pathways in directing
Mks response in term of cell spreading, migration, platelet release
and fibronectin assembly. This different behavior seems to be
related to the different nano-mechanical properties of modified
collagen with respect to native protein. In particular, N-acetylation
of lysine side chains of collagen blocks the formation of
banded fibrils and self-aggregation leading to differences in the in
vitro sopramolecular organization. Atomic force microscopy
analysis of Mks interaction with collagens clearly demonstrated
that absence of fibrils, despite similar integrin engagement, and
different mechanical properties of these proteins, regulate Mks
behaviour and fate. New insights into signaling pathways and in
mechano-sensing systems of cells need to be addressed but nanoscale
mechanical properties of ECMs seem to have an important
role in regulating megakaryocyte behavior in vitro and probably
in vivo
