The Functional Response of Mesenchymal Stem Cells to Electron‐Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity

Abstract

Biggs, M. J. P. et al. (2017) The functional response of mesenchymal stem cells to electron-beam patterned elastomeric surfaces presenting micrometer to nanoscale heterogeneous rigidity. Advanced Materials, 29(39), 1702119.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.Biggs, M. J.P. et al. (2017) AbstractCells directly probe and respond to the physicomechanical properties of their extracellular environment, a dynamic process which has been shown to play a key role in regulating both cellular adhesive processes and differential cellular function. Recent studies indicate that stem cells show lineage-specific differentiation when cultured on substrates approximating the stiffness profiles of specific tissues. Although tissues are associated with ranging Young's modulus values for bulk rigidity, at the sub-cellular level, and particularly at the micro-and nanoscales, tissues are comprised of heterogeneous distributions of rigidity.Lithographic processes have been widely explored in cell biology for the generation of analytical substrates to probe cellular physicomechanical responses. In this work, we show for the first time that that direct-write e-beam exposure can significantly alter the rigidity of elastomeric PDMS substrates and develop a new class of two-dimensional elastomeric substrates with controlled patterned rigidity ranging from the micron to the nanoscale. The mechano-response of human mesenchymal stem cells to e-beam patterned substrates was subsequently probed in vitro and significant modulation of focal adhesion formation and osteochondral lineage commitment was observed as a function of both feature diameter and rigidity, establishing the groundwork for a new generation of biomimetic material interfaces.3

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…Electron‐beam lithography can have significantly higher resolution (sub‐50 nm) than photolithographic processes but comes at the cost of long patterning times and limited write areas. As such it provides a useful research tool, e.g., patterning small regions to study a limited number of cells, but is not normally feasible where large culture areas are required (e.g., in high‐throughput assays). One potential mitigation is to use electron‐beam lithography to define a master stamp, which is then replicated repeatedly using imprint techniques, as discussed below.…”

Characterization of Cells Interactions with Patterned Azopolymer-Based Materials using SEM, AFM and Video Microscopy

“…The cellular mechanical response to the photostructured surfaces had an amplitude modulated surface with a typical pitch of 800 nm and a depth of 100 nm. Probably, as it was previously demonstrated [11], the sensing apparatus of cellular rigidity can also detect discrete sub-micrometer discrepancies in the polymer matrix rigidity. The amplitude modulation of the azopolymer surface is the place for local modulation of the Young modulus due to the photo-induced modification of the material mechanical properties during the trans-cis isomerization [12,13].…”

An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal‐Ion–Ligand Coordination Regulates the Mechanosensing and Differentiation of Stem Cells

“…Cellular adhesion and functions are regulated by interactions between cells and bioactive moieties . Dynamic binding between integrin receptors and cell‐adhesive bioactive moieties leads to the formation of focal adhesions (FAs) that mediate cell adhesion and mechanotransduction . Developing materials with cell‐adhesive bioactive moieties can allow the regulation of diverse and reversible cell–material interactions, such as cell adhesion, release, and differentiation.…”