Abstract
Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here, we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues, including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over approximately a 24 h period after seeding the cells in the specific environment and uses the cytoskeletal free-energy distribution to forecast the lineage the hMSCs will commit to. The cytoskeletal free energy which succinctly parametrizes the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt.
Highlights
IntroductionStem cells have the dual ability to differentiate into various mature cells (such as osteoblasts, chondrocytes, neuroblasts, etc.) that form various tissues, and proliferate to maintain a pool of immature cells that can differentiate when required
Stem cells have the dual ability to differentiate into various mature cells that form various tissues, and proliferate to maintain a pool of immature cells that can differentiate when required
We shall consider the response of human mesenchymal stem cells (hMSCs) in both growth media and mixed media when seeded on elastic substrates of varying stiffness and on effectively rigid substrates patterned with adhesive islands
Summary
Stem cells have the dual ability to differentiate into various mature cells (such as osteoblasts, chondrocytes, neuroblasts, etc.) that form various tissues, and proliferate to maintain a pool of immature cells that can differentiate when required. While the effect of soluble factors on stem cell lineage commitment and differentiation has been extensively studied, a thorough investigation of the influence of insoluble signals such as ECM rigidity and adhesive properties of the substrate is still ongoing. It is well known that environmental cues such as microgravity [5] and mechanical cues such as substrate rigidity, substrate curvature, arrangements of micropillars, gratings and wells [6,7,8,9] dictate cell fate Nanoscale physical cues such as nanotubes and nanowires of different pore sizes and spacing, nano-grating, nano-posts and different arrangements of nano-pits [10,11,12,13,14] act at the scale of single focal adhesions to set cell lineage. Several models have been developed and refined using the wealth of information provided by experiments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
