Multiscale Biomimetic Topography for the Alignment of Neonatal and Embryonic Stem Cell-Derived Heart Cells

Abstract

Nano-and microscale topographical cues play critical roles in the induction and maintenance of various cellular functions, including morphology, adhesion, gene regulation, and communication. Recent studies indicate that structure and function at the heart tissue level is exquisitely sensitive to mechanical cues at the nano-scale as well as at the microscale level. Although fabrication methods exist for generating topographical features for cell culture, current techniques, especially those with nanoscale resolution, are typically complex, prohibitively expensive, and not accessible to most biology laboratories. Here, we present a tunable culture platform comprised of biomimetic wrinkles that simulate the heart's complex anisotropic and multiscale architecture for facile and robust cardiac cell alignment. We demonstrate the cellular and subcellular alignment of both neonatal mouse cardiomyocytes as well as those derived from human embryonic stem cells. By mimicking the fibrillar network of the extracellular matrix, this system enables monitoring of protein localization in real time and therefore the high-resolution study of phenotypic and physiologic responses to in-vivo like topographical cues.

Mesenchymal stem cell mechanobiology and emerging experimental platforms

“…The effects of ordered versus disordered features also raises interesting questions related to potential roles of symmetry and disorder in vivo. As experimental cell biology embraces heuristic approaches to problem solving, the use of multiscale and variously ordered topographies will increasingly be used to study cell fate in complex environments [172]. The trend towards larger sample numbers and combinatorial experiments require increasingly sophisticated data acquisition, statistical analysis [79] and systems biology modelling efforts [173].…”

Tissue Engineering: Construction of a Multicellular 3D Scaffold for the Delivery of Layered Cell Sheets

“…The pretreated thermo-sensitive plates can also be used for creating the cell sheets. Special topological surfaces are used to specifically pattern (i.e., align) the cells 30 .…”

Human Pluripotent Stem Cells in Cardiovascular Research and Regenerative Medicine

“…To more closely recapitulate the in vivo environment of the heart, various groups have used different approaches to manipulate the surface and geometry of the culture platform, cell and matrix composition. For instance, Luna et al used a tunable culture platform comprised of biomimetic wrinkles to simulate the heart's complex anisotropic and multiscale architecture and showed that the hESC-CMs cultured on these 'microgrooved' substrates display the typical tropomyosin banding pattern consistent with organized sarcomeric structure patterns (Luna et al, 2011) (Figure 4, adopted with permission from Luna et al 2011 Tissue Eng Part C Methods Vol. 17, No.…”