The Pertinent Role of Cell and Matrix Mechanics in Cell Adhesion and Migration.

Abstract

The processes of cell adhesion and migration fulfill crucial tasks during physiological developmental processes, immune responses, angiogenesis, or tissue injury and pathological diseased states including the cancer, cancer angiogenesis and its malignant progression, referred to as metastasis. Thereby, the cells undergo tremendous alterations that obviously lead to pronounced morphological alterations that are closely coupled to intracellular structural changes and mechanical perturbations (Humphrey et al., 2002; Guck et al., 2005; Mierke et al., 2008a, 2011; Kumar and Weaver, 2009; Menon and Beningo, 2011; Lekka et al., 2012; Humphries et al., 2019; Mierke, 2019a). These alterations occur on different cellular length scales, such as bulk alterations, compartmental alterations, structural compositional changes, molecular alterations down to gene expression regulatory events. All of these types of changes cannot be treated as purely separate events that can be fully deciphered in an independent manner. Hence, the specific microenvironmental constraints play a prominent role in unraveling the impact of the intricate interplay. Due to the vastly high number of molecules that function in cell adhesion under physiological and pathological processes, the agglomeration of proteins within focal adhesion has been termed cancer cellular adhesome to discriminate them from randomly distributed surrounding proteins (Maziveyi and Alahari, 2017). The contributing proteins of the adhesome can be divided into four different branches of the basic adhesion system which includes the Talin-Vinculin (Mierke et al., 2008a, 2010; Golji et al., 2011; Wang et al., 2019; Boujemaa-Paterski et al., 2020), FAK-Paxillin (Hu et al., 2015; Mierke et al., 2017; Ripamonti et al., 2021), α-Actinin-Zyxin-VASP (Oldenburg et al., 2015), and ILK-PINCH-Kindlin biochemical signal transduction pathways (Honda et al., 2013; Horton et al., 2015; Kunschmann et al., 2017). All of them represent critical pathways or mechanosensory systems to respond to changes in the mechanical homoestatic stage of cells. There are also additional organizational structures such as protrusions, podosomes, invadosomes, and similar structures for the motile function or migratory capacity of cells. When these structures, such as invadopodia are altered, the process of cancer metastasis can be impaired, such as for melanoma cells (Karamanou et al., 2021). Cancer cells act in various types of directional cell migration compromising chemotaxis (chemoattractant gradient), haptotaxis (environmental gradient), electrotaxis (ionic flux), galvanotaxis (electrical attractant), pilotaxis, and durotaxis (rigidity attractant) (Roussos et al., 2011; Allen et al., 2013; Mierke, 2021). Recognition of the microenvironment by cancer cells allows them to translate diverse signaling conveyed through focal adhesions. The stiffness produced by the extracellular matrix initiates and synergizes with the cell-matrix forces imposed by the cells (Krieg et al., 2008). Cells are able to capture multiple properties of the extracellular matrix in terms of stiffness and analysis of anisotropy (Geiger et al., 2009).