Progressive Myofibril Reorganization of Human Cardiomyocytes on a Dynamic Nanotopographic Substrate

Abstract

Cardiomyocyte (CM) alignment with striated myofibril organization is developed during early cardiac organogenesis. Previous work has successfully achieved in vitro CM alignment using a variety of biomaterial scaffolds and substrates with static topographic features. However, the cellular processes that occur during the response of CMs to dynamic surface topographic changes, which may provide a model of in vivo developmental progress of CM alignment within embryonic myocardium, remains poorly understood. To gain insights into these cellular processes involved in the response of CMs to dynamic topographic changes, we developed a dynamic topographic substrate that employs a shape memory polymer coated with polyelectrolyte multilayers to produce a flat-to-wrinkle surface transition when triggered by a change in incubation temperature. Using this system, we investigated cellular morphological alignment and intracellular myofibril reorganization in response to the dynamic wrinkle formation. Hence, we identified the progressive cellular processes of human-induced pluripotent stem cell-CMs in a time-dependent manner, which could provide a foundation for a mechanistic model of cardiac myofibril reorganization in response to extracellular microenvironment changes.

Stem Cell Mechanobiology and the Role of Biomaterials in Governing Mechanotransduction and Matrix Production for Tissue Regeneration

“…A dynamic topographic substrate was developed using a polyelectrolyte multilayer (PEM) coated shape memory polymer (SMP), which upon change in incubation temperature transitions from a flat-to-wrinkle configuration inducing a change in morphology but no change in stiffness (Sun et al, 2020). The specific objective was to investigate the progressive remodeling of human iPSC-CMs seeded onto SMP-PEM substrates within a 24-hour period.…”

“…With regards to intracellular myofibril reorganization, the sarcomere index decreased early in the culture period and vinculin length decreased at early time points (hour 4 and 8) but returned to the original length at hour 12. Thin filament length and the sarcomere length increased late in the culture period (16-24 h) (Sun et al, 2020). Thus it was proposed that hiPSC-CM processes respond to dynamic structural cues from cell microenvironment.…”

Manipulation of Stem Cells Fates: The Master and Multifaceted Roles of Biophysical Cues of Biomaterials

“…Reproduced with permission. [ 63 ] Copyright 2020, American Chemical Society. D) Light‐induced reshaping of azopolymer 3D structures from circular nanopillar to elongated nanobar and dynamic control of cell membrane via actinpolymerization.…”

“…The iPSCs‐CMs exhibited oriented alignment of cell and nuclei shape, as well as myofibril reorganization, in response to the dynamic topographic changes (Figure 3C). [ 63 ] This enhancement is conductive to CM contractility and makes the reported material a satisfactory alternative for cardiac tissue repair.…”

“…Shape memory polymer (SMP) is another type of cutting‐edge material that can deform upon receiving external stimuli such as light [ 68 ] or heat [ 63 ] and can recover its original shape in a time‐dependent manner. Recently, researchers have utilized thermo‐responsive SMP, which generates a dynamic flat‐to‐wrinkle transition, to investigate NSC differentiation and hiPSC alignment in a dynamic microenvironment.…”