Individually programmable cell stretching microwell arrays actuated by a Braille display

Abstract

Cell culture systems are often static and are therefore nonphysiological. In vivo, many cells are exposed to dynamic surroundings that stimulate cellular responses in a process known as mechanotransduction. To recreate this environment, stretchable cell culture substrate systems have been developed, however, these systems are limited by being macroscopic and low throughput. We have developed a device consisting of 24 miniature cell stretching chambers with flexible bottom membranes that are deformed using the computer-controlled, piezoelectrically actuated pins of a Braille display. We have also developed efficient image capture and analysis protocols to quantify morphological responses of the cells to applied strain. Human dermal microvascular endothelial cells (HDMECs) were found to show increasing degrees of alignment and elongation perpendicular to the radial strain in response to cyclic stretch at increasing frequencies of 0.2, 1, and 5 Hz, after 2, 4, and 12h. Mouse myogenic C2C12 cells were also found to align in response to the stretch, while A549 human lung adenocarcinoma epithelial cells did not respond to stretch.

Engineering Muscle Tissues on Microstructured Polyelectrolyte Multilayer Films

“…12 Mechanical tension and stretching can also contribute to myoblast alignment, fusion, and maturation. 13,14 In the present study, we aimed at controlling the alignment of myotubes in vitro and at investigating nuclear orientation by combining a microstructured substrate for guiding cell adhesion and differentiation with a thin film coating with tunable mechanical properties.…”

Mesenchymal stem cell mechanobiology and emerging experimental platforms

“…Historically, these have been achieved by varying substrate elasticity [69][70][71] or adhesive properties that direct cell shape (figure 2b) [13,15,72]; both methods are well suited for miniaturized array-based HTS platforms. Dynamic mechanical loading (figure 2c) is often more challenging to implement than mechanically static cultures but is nevertheless increasingly represented in microfabricated platforms [59,[73][74][75][76].…”

“…Deformable elastomeric membranes are proving useful for this purpose [59,73,74,133,134] (figure 5). As shown in figure 5a, pressure supplied through dedicated channel networks deforms overlying elastomeric structures and thereby transfers mechanical loads to samples for cell stretching [59,74] or compression of arrayed biomaterials (figure 5b) [73]. Standard soft-lithography methods are used to produce membrane arrays that simultaneously apply a range of strains (figure 5c) that can be measured in situ using integrated elastomeric strain sensors (figure 5d).…”

Flip channel: A microfluidic device for uniform-sized embryoid body formation and differentiation

“…[12][13][14][15][16][17][18][19][20] Moreover, a microfluidic device capable of precisely positioning EBs to study their differentiation under various controlled a) Author to whom correspondence should be addressed. Electronic mail: tungy@gate.sinica.edu.tw.…”