Exploring how polyacrylamide and PDMS materials are transforming our understanding of cardiac cell behavior through tunable mechanical properties
Every day, the human heart beats approximately 100,000 times, pumping blood throughout our bodies with remarkable reliability. This vital organ possesses an often-overlooked characteristic: it's exquisitely sensitive to its mechanical environment. The physical properties of the surrounding tissue influence everything from how heart cells beat to how they metabolize energy.
For decades, scientists have studied cardiac cells on stiff plastic and glass surfaces that bear little resemblance to the natural cardiac environment.
Tunable polymers like polyacrylamide (PAA) and polydimethylsiloxane (PDMS) are creating environments that mimic natural heart tissue.
This fundamental mismatch has obscured crucial biological insights and hampered drug development for cardiovascular diseases, which remain a leading cause of death worldwide 4 .
Cardiac cells, particularly cardiomyocytes (the contracting cells of the heart) and cardiac fibroblasts (the structural supporting cells), are highly mechanosensitive. They constantly sense and respond to the stiffness, elasticity, and chemical properties of their surroundings through a process called mechanotransduction 1 .
Traditional cell culture methods use plastic or glass substrates with stiffness values in the gigapascal range—literally millions of times stiffer than natural heart tissue 3 .
When sensitive cardiac cells are placed on these unnaturally hard surfaces, they experience fundamental changes in their structure, beating patterns, and metabolic processes.
Stem cell-derived cardiomyocytes cultured on traditional plastic substrates displayed pathological metabolism, calling into question the physiological relevance of findings from such systems 3 .
Polyacrylamide (PAA) hydrogels have emerged as a powerful tool in cardiac research due to their highly tunable mechanical properties. By adjusting the ratio of acrylamide monomers to bis-acrylamide crosslinkers, researchers can precisely control the stiffness of the resulting gel across the physiological and pathological range of heart tissue 8 .
Because PAA is naturally protein-repellent, researchers must chemically modify its surface to allow cardiac cells to adhere. Several strategies have been developed to address this challenge 8 .
Photoactivatable crosslinker for protein attachment, expensive but effective
Converts amide groups to hydrazide groups for protein binding
Incorporated during gel fabrication to create binding sites
Polydimethylsiloxane (PDMS) is a silicone-based polymer with unique rheological properties—it can behave like a viscous liquid or an elastic solid depending on the conditions .
PDMS is particularly well-suited for cardiac research because it can be tuned to match cardiac stiffnesses by adjusting the ratio of base polymer to curing agent or by blending different PDMS formulations 3 .
The real power of PDMS emerges in advanced microphysiological systems where it serves as both the substrate and structural material for intricate microfluidic devices.
A compelling 2025 study led by Patel and colleagues investigated a crucial question: how does the stiffness of the culture substrate influence the energy metabolism of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) 3 .
The healthy adult heart derives approximately 95% of its ATP from fatty acid oxidation, while diseased hearts revert to a fetal metabolic pattern that relies more heavily on glucose—a phenomenon known as metabolic reprogramming 3 .
The researchers hypothesized that the pathological stiffening of heart tissue in diseases might directly contribute to this metabolic shift.
Created PDMS substrates with stiffnesses of 20 kPa and 130 kPa by mixing different mass ratios of Sylgard elastomers 3 .
iPSC cells were differentiated into ventricular cardiomyocytes using an established protocol 3 .
iPSC-CMs were transferred onto experimental substrates and cultured until day 25 for maturation 3 .
Used isotope-labeled GC-MS and extracellular flux analysis to track metabolic pathways 3 .
The findings were striking. Cardiomyocytes cultured on traditional plastic substrates demonstrated significantly greater utilization of glucose and increased lactic acid efflux—indicative of enhanced glycolytic activity and a shift toward aerobic glycolysis as the primary ATP source 3 .
| Substrate Type | Stiffness | Primary Metabolic Pathway | Metabolic State |
|---|---|---|---|
| Plastic/Glass | 1-70 GPa | Glycolysis | Pathological |
| 130 kPa PDMS | 130 kPa | Mixed Glycolysis/Oxidation | Early Disease |
| 20 kPa PDMS | 20 kPa | Fatty Acid Oxidation | Physiological |
This research demonstrated that culturing cardiomyocytes on traditional plastic or glass substrates—the standard approach for decades—fundamentally alters their metabolic function, potentially compromising the physiological relevance of experimental findings 3 .
The advancement of our understanding of cardiac cell behavior relies on specialized materials and reagents carefully engineered to mimic physiological conditions.
| Tool/Material | Primary Function | Key Characteristics |
|---|---|---|
| Polyacrylamide (PAA) | Tunable substrate for 2D cell culture | Precise stiffness control, optical transparency, requires functionalization |
| Polydimethylsiloxane (PDMS) | Substrate for 2D culture and 3D microfluidic devices | Gas permeability, tunable elasticity, biocompatibility |
| Sulfo-SANPAH | PAA functionalization | Photoactivatable crosslinker for protein attachment, expensive but effective |
| Sylgard 527 & 184 | PDMS formulation | Silicone elastomers mixed in ratios to achieve desired stiffness |
| Geltrex/Matrigel | Substrate coating | Basement membrane extract that promotes cell adhesion |
| Gelatin | PDMS coating | Natural polymer that improves cell attachment to PDMS |
| Isotope-labeled Metabolites | Metabolic tracking | 13C-glucose or 13C-fatty acids to trace metabolic pathways |
The growing understanding of how cardiac cells respond to their mechanical environment represents a paradigm shift in cardiovascular research.
The traditional approach of culturing heart cells on impossibly stiff plastic surfaces is gradually giving way to more physiologically relevant systems using tunable materials like PAA and PDMS. These advanced platforms have revealed crucial insights into how mechanical cues influence everything from cardiac metabolism to fibroblast activation—insights that were previously obscured by inappropriate culture conditions.
Combining tunable materials with microfluidic delivery, mechanical stretching, and multiple cell types to create accurate heart models 4 .
Materials that can dynamically change properties in response to external stimuli or deliver therapeutic agents 4 .
More accurate systems for drug testing and safety assessment to accelerate cardiovascular treatment development.
"As the famous saying goes, 'we shape our tools and thereafter our tools shape us.' In cardiovascular research, we're now learning that to truly understand the heart, we need to provide it with the right mechanical environment—one beat at a time."