Mechanical Properties of Soft Biological Membranes for Organ-on-a-Chip Assessed by Bulge Test and AFM

Abstract

Advanced in vitro models called “organ-on-a-chip” can mimic the specific cellular environment found in various tissues. Many of these models include a thin, sometimes flexible, membrane aimed at mimicking the extracellular matrix (ECM) scaffold of in vivo barriers. These membranes are often made of polydimethylsiloxane (PDMS), a silicone rubber that poorly mimics the chemical and physical properties of the basal membrane. However, the ECM and its mechanical properties play a key role in the homeostasis of a tissue. Here, we report about biological membranes with a composition and mechanical properties similar to those found in vivo. Two types of collagen-elastin (CE) membranes were produced: vitrified and nonvitrified (called “hydrogel membrane”). Their mechanical properties were characterized using the bulge test method. The results were compared using atomic force microscopy (AFM), a standard technique used to evaluate the Young’s modulus of soft materials at the nanoscale. Our results show that CE membranes with stiffnesses ranging from several hundred of kPa down to 1 kPa can be produced by tuning the CE ratio, the production mode (vitrified or not), and/or certain parameters such as temperature. The Young’s modulus can easily be determined using the bulge test. This method is a robust and reproducible to determine membrane stiffness, even for soft membranes, which are more difficult to assess by AFM. Assessment of the impact of substrate stiffness on the spread of human fibroblasts on these surfaces showed that cell spread is lower on softer surfaces than on stiffer surfaces.

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

“…Likewise, the mechanical properties of the membranes are also an important parameter to provide similar properties to those found in vivo conditions. [ 32 ]…”

Alveolus Lung-on-a-Chip Platform: A Proposal

“…Zamprodogno et al (2021) created a thin, elastic, biological membrane by drop-casting a collagen-elastin solution onto a thin gold mesh with a poresize of 260 µm that supports the array of 40 alveoli [66]. This membrane showed a good performance, enabling the recreation of the air-liquid interface and application of mechanical stretch to reproduce respiratory motions.…”

“…Several groups have created lung airway-on-a-chip, aiming to model lung physiology and diseases that primarily affect the airways, such as asthma or COPD [66][67][68][69]. Sellgren et al (2014) created a biomimetic microfluidic device composed of three individually accessible and vertically stacked compartments, separated from each other by a synthetic nanoporous membrane [67].…”

3D printed lung on a chip device with a stretchable nanofibrous membrane for modeling ventilator induced lung injury

“…15 While these membranes were stretchable up to 10%, the ECM hydrogel was fabricated using spontaneous thermal assembly of ECM molecules and thus lacked covalent crosslinking between ECM molecules, which rendered them somewhat mechanically weak and unable to mimic VILI where stretching exceeds 20%. 18, 21-23…”

“…15 While these membranes were stretchable up to 10%, the ECM hydrogel was fabricated using spontaneous thermal assembly of ECM molecules and thus lacked covalent crosslinking between ECM molecules, which rendered them somewhat mechanically weak and unable to mimic VILI where stretching exceeds 20%. 18,[21][22][23] Therefore, materials which can satisfy the multiple critical aspects of the lung are needed; namely nanofibrous topography which supports cell growth while allowing for mechanical stretch in the range of that encountered during normal and pathologic scenarios. Electrospun membranes are one potential option due to the fact that they are made of micro-or nanofibers, where the electrospinning parameters and the material can be chosen to generate membranes with specific mechanical properties.…”