BioAFM Journal Club

Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury

by Tomohiro Yokota, Jackie McCourt, Feiyang Ma, Marcus Seldin, Aldons J. Lusis, Arjun Deb et al.

Cell Volume 182, ISSUE 3, P545-562.e23, August 06, 2020 
DOI: 10.1016/j.cell.2020.06.030

In this article, researchers aimed to investigate which (mechanosensitive) factors influence the size of scar tissue after heart injury and how the murine models of acute ischemic cardiac injury can be used to improve the regulation of wound healing.

To determine the stiffness of mid-ventricular scar tissue 7 days after injury, atomic force microscopy (AFM) measurements were performed on cardiac tissue cryosections using a JPK NanoWizard 4A BioAFM with a 200 x 200 x 200 µm HybridStage combined with a fluorescence Leica M205 stereoscope. Both scar and non-scar regions were identified with collagen I dense immunofluorescence and were probed with cantilevers with a 10 µm sphere (stiffness of 0.14 N/m) in force spectroscopy mode.

The authors found that the Young’s modulus was significantly lower (15%) in Col5a1CKO animals. Furthermore, they reported that Collagen V deficiency leads to a change in the mechanical properties of scars and, more specifically, to an increase in scar size after acute heart injury. Altered mechanosensitive cues augment myofibroblast formation in scar. If the surrounding matrix is less stiff, cardiac fibroblasts cannot transduce contractile forces to shrink the size of the scar. However, inhibition of specific integrins prevents increased scarring in Col-V-deficient states.