Angiogenesis and Immunomechanics
Healing begins with the self-organisation of cells in the wound to reestablish structured tissue and restore the mechanical stability and intrinsic pretension of the injured matrix lost through the injury. Our aim is to decipher this independent organisation of fibroblasts, vascular precursors, immune cells and mechanical instability in the complex environment of the tissue. A better understanding of this interplay forms the basis for novel therapeutic approaches in musculoskeletal regeneration.
You are here:
Fibronectin binding peptide as mechanosensor to detect tensional state of fibronectin in regenerating tissues
Extracellular matrix (ECM) remodeling in regenerative processes is well documented, yet, the underlying mechanism how local strains of single ECM fibers drive this process remains unknown. This is due to the fact that not a single probe to either measure forces or force-induced molecular strains in tissues exists today that is applicable to be used in vivo or in histological tissue sections ex vivo. We here want to introduce a new mechanosensitive probe to visualize the tensional state of ECM fibers to gain a more pronounced understanding of the complexity of the ECM and how ECM alterations correlate to tissue functions. Bacterial fibronectin binding peptides (FnBP) were found to be a promising mechanosensitive probe to detect the tensional state of fibronectin. Fibronectin is the most abundant protein in the ECM and exhibits many binding sites for other ECM proteins, growth factors and cells (figure 1). Depending on the cellular force that is applied to individual fibronectin fibers and the overall composition of the ECM, fibronectin can be either in a stretched or relaxed form. FnBP specifically recognizes the N-terminal fibronectin type I domain (figure 1) and exhibits nM binding affinity to relaxed, but not stretched fibronectin fibers (figure 2). Applying that novel mechanosensitive tool on ex vivo bone sections, we are especially aiming to better understand the underlying mechanism of bone regeneration and how local strains of fibronectin fibers drive this process.