Effect of Nuclear Stiffness on Cell Mechanics and Migration of Human Breast Cancer Cells

Inhomogeneities in 3D Collagen Matrices Impact Matrix Mechanics and Cancer Cell Migration

“…In accordance with existing studies, we have shown that both stiffness and pore size govern the invasion of cancer cells into 3D-enclosed matrices ( Wolf and Friedl, 2011 ; Lang et al, 2015 ; Sapudom et al, 2015 ; Fischer et al, 2017 , 2020 ). These parameters are eligible to roughly describe the interplay of cancer cell invasion with the microenvironment on a global level.…”

“…The invasion of cancer cells is a complex process. The change of the cell shape (Lyons et al, 2016;Baskaran et al, 2020), the softening the cell body and/or the nucleus (Fischer et al, 2020), the enzymatic-degradation of the matrix (Gialeli et al, 2011;Wolf and Friedl, 2011), the switch between migration modes (Friedl and Wolf, 2010) are some of well-founded methods that cancer cells use to overcome steric barriers and thus efficiently invade confined networks.…”

“…Networks that are more homogeneous could be invaded significantly deeper by highly invasive MDA-MB-231 cancer cells, which predominantly prefer adhesion-based mesenchymal invasion. Mostly highly invasive cancer cells utilize strong adherence dependent mechanisms, which is observable e.g., by pronounced fiber displacements ( Fischer et al, 2017 ), to squeeze through narrow confinements accompanied by several intracellular deforming mechanisms ( Krause and Wolf, 2015 ; Fischer et al, 2020 ). We hypothesized that these mechanisms could be applied most efficiently to a homogeneous scaffold.…”

“…We analyzed the pore size of the collagen matrices as previously described (Fischer et al, 2020) based on a custom-built python program already published (Fischer et al, 2019). In more detail, polymerized collagen matrices were stained overnight with TAMRA-SE (Sigma-Aldrich, Cat.…”

“…Since hydrogels are used to investigate cancer cell behavior, collagen type I from bovine dermis and rat tail tendon are prominently employed for matrix engineering ( Brown, 1982 ; Behrens et al, 1989 ; Liebersbach and Sanderson, 1994 ; Friedl et al, 1997 ; Wolf et al, 2009 , 2013 ; Willis et al, 2013 ; Mohammadi et al, 2015 ; Sapudom et al, 2015 , 2019 ; Krause et al, 2019 ). In many cases, even mixtures of rat and bovine collagen are used ( Koch et al, 2012 ; Lang et al, 2015 ; Lautscham et al, 2015 ; Fischer et al, 2017 , 2020 ; Kunschmann et al, 2019 ; Riedel et al, 2019 ; Sauer et al, 2019 ; Mierke et al, 2020 ). Although those collagen matrices are made of the same type of collagen (namely type I), they can assemble to a totally different network exhibiting different physical properties ( Wolf et al, 2009 ; Paul et al, 2016 ).…”