Table 3.

Highlights of mechanical cues influencing cell fate. *High throughput not shown in the paper but could be easily developed.

Physical Manipulation Technique	Cellularity Level	Dimension	Physical Cue Modulated	Effect of Physical Cue Modulation	Throughput	Reference
Micropatterning	Single Cells	2D	Cell size	Endothelial cell apoptosis is inversely related to cell spreading area.	High*	Chen et al. 1997
			Cell shape	Constraining MSC culture area within pentagons with concave lines or in shapes with high aspect ratios promotes osteogenic differentiation due to increased actomyosin contractility.	High*	Kilian et al. 2010
	Cell Colonies	2D	Perimeter topology	Melanoma cells occupying larger arc angles at the tumour periphery demonstrate greater tumorigenicity due to hypoxia-induced mechanotransduction.	High*	Lee et al. 2017
			Colony size	Colonies of larger diameters allow maintenance of human PSC pluripotency and can further be used as a platform to study early PSC fate in response to specific chemical cues.	High	Nazareth et al. 2013
				Mediated by colony boundary, not size, human PSCs organize into radially segregated germ layer regions in response of BMP4.	High	Warmflash et al. 2014 Tewary et al. 2017
	Organoids	3D	Organoid shape (surface area: volume ratio) using microfibres	Increased patterning and organization of cerebral organoids grown around microfibres lead to mature neuronal features.	Low	Lancaster et al. 2017
			Cell position via micromoulding	Geometry of hollow tubules reliably predict branching patterns of mammary epithelia through mechanical stress gradients, and further reveal mechanisms of cellular rearrangement.	Low	Nelson et al. 2006, 2008 Mori et al. 2009 Gjorevski and Nelson 2010
			Cell curvature through micromoulding	Tubular diameters exert differential cellular tension and thereby dictate cell fate of bipotent lung progenitors.	Low	Soleas et al. 2020
Substrate Topography	Multiple cells	2D	Cell position in response to undulation	Epidermis-inspired topography induces human keratinocytes to pattern into distinct regions of progenitor, differentiating, and proliferating cells, as seen in vivo.	Low- Medium	Viswanathan et al. 2016
	Single Cells/ Cell Patches	2D	Cell shape via “TopoChip” topographies	Smaller feature size is most essential for maintaining human PSC pluripotency.	High	Unadkat et al. 2011 Reimer et al. 2016
	Single Cells/ Cell Clusters/ Monolayer	2D	Cell shape via grooves (nano to micro scale)	Due to actomyosin contractility, neuronal differentiation is promoted on anisotropic nanoscale grooves in a highly expedited manner compared to standard protocols.	High	Ankam et al. 2013, 2015
	Single Cells/ Cell Patches	2D	Cell shape via grooves (micro scale)	Associated with cell morphology and focal adhesion formation, wider groove ridges promote adipogenic differentiation, while thinner ridges promote osteogenic differentiation of MSCs.	High*	Abagnale et al. 2015
	Single Cells/ Cell Patches/ Cell Colonies	2D	Colony shape via grooves (nano scale)	Linked to differential YAP and TAZ activity, grooves elongate human PSC colonies which maintain pluripotency and are highly responsive to morphogenic differentiation cues.	High*	Abagnale et al. 2017