Changes in cellular mechanical properties during onset or progression of colorectal cancer

Table 2 List of cell properties that depends on substrate stiffness

Substrate-related mechanical properties	Substrate stiffness	Substrate type and composition	Outcomes	Related-biochemical and genetic pathway	Ref.
E-to-R transition	1 kPa	Laminin	The E to R transition is not observed.	Not applicable.	Tang et al[24], 2015
		or fibronectin coated PA gel
	21 kPa	Laminin coated PA gel	Approximately 70%-90% of E cells start transiting to R cells after culturing for 7 d. Transition takes approximately 5-10 h.	E-Cadherin decreases in dissociated
				R cell by a factor 4.73 ± 1.4.
		Fibronectin coated PA gel	Approximately 70%-90% of E cells start transiting to R cells after culturing for 15 d. Transition takes approximately 5-10 h.	Replanted cells retain their dissociated phenotype irrespective of the substrate stiffness.
	3.6 GPa	Fibronectin coated PA gel	Not observed.	Not applicable.
	20 kPa	E-cadherin coated PA gel	E cells transit to R cells in 6 h.	Vinculin in mainly located at the cell-cell junction.
		Fibronectin coated PA gel	E cells transit to R cells in 6 h.	Vinculin in mainly located at the cell- substrate junction.	Ali et al[45], 2014
	~70 GPa	E-cadherin coated stiff glass substrates	Transition is not observed.	Not applicable.
	Extremely stiff1	Plastic/glass stiff substrate	Occasionally E cells transit to R cell (1 cell over 2 × 105).	R cells are deficient in αE-catenin (protein linking the cell-cell adhesion molecule E-cadherin to the action cytoskeleton).	Vermeulen et al[46-48], 1995, 1998, 1999
Cell colony sizes	1-20 kPa	Gradient stiffness fibronectin coated PA gel	E type: colony size positively correlated with substrate stiffness	Not applicable.	Tang et al[25], 2012
			R type: colony size (smaller than E-colony size) positively correlated with substrate stiffness.
	Soft1	Agar gel	Equal numbers of E and R cells were plated and examined after 10 d, 75% of the E cells plated formed colonies while R cells formed no colonies.		Rosenthal et al[72], 1977
Adhesion	1-20 kPa	Gradient stiffness fibronectin coated PA gel	E type: cells show a strong cell-cell adhesion and cell-substrate adhesion evaluated through the measurement of the cell-substrate contact area (188.1 ± 80.7 μm2) by confocal microscopy. Moreover, a strong aspecific adhesion of ~250 nN is detected trough a novel MEMS system.	Reduced E-cadherin expression on R cells.	Tang et al[25], 2012
			R type: cells show a weak cell-cell adhesion on very soft substrate (1 kPa). No cell-cell contact is observed on stiffer substrate (5-10-15-20 kPa). A weak cell/substrate adhesion is demonstrated through the measurement of the cell/surface contact area (49.5 ± 20.9 μm2).
			A week aspecific adhesion of ~2.5 nN is measured through a MEMS system.

¹Young’s modulus not provide.