In recent years, alongside biological cues, significant attention has been paid to the influence of biomechanics on cellular function. Studies have systematically demonstrated that physical stimuli from the matrix—such as deformability, stiffness, contraction/stretch, and external pressures—regulate cellular behavior in a spatial and temporal context within living organisms. Mechanotransduction, the process through which cells convert mechanical stimuli into biochemical signals, is hypothesized to involve force transmission through bound proteins, leading to conformational changes that influence cell signaling, gene expression, phenotype, and function.

The impact of biomechanics on pharmacological effects is well-documented. We propose that drug testing can be significantly improved by using cells that exhibit the most (patho)physiologically relevant phenotypes, thereby ensuring that assays replicate the biomechanical environment pertinent to the condition being treated.

It is extensively documented that cellular responses to pharmacological agents differ when subjected to biomimetic mechanical stimulation as opposed to a conventional static environment. For instance, studies have shown that kidney cells cultured under microfluidic conditions with fluid shear exhibit increased sensitivity to nephrotoxic drugs compared to static conditions. Similarly, in a peristalsis model, both colon cancer and non-cancer cells displayed reduced uptake of nanoparticles compared to non-peristalsis conditions, leading to decreased efficacy in tumor treatment. Additionally, several genes whose expression is influenced by mechanical pressures are related to medication resistance. These findings highlight the importance of considering biomechanical cues when screening and evaluating drugs or nanoparticles.

With advances in biomaterials, microfabrication, and microfluidic technologies, next-generation methodologies such as 3D organoid culture, 3D bioprinting, organ-on-a-chip, organoid-on-a-chip, and other biomechanical techniques aim to replicate tissue architectures, morphologies, functions, and biophysical cues to emulate the in vivo cellular environment. The integration of biological and biomechanical methods offers significant advantages for pharmacological research, providing enhanced simulations of the drug interaction environment and yielding more precise gene profile data compared to traditional cell culture methods. These innovations represent promising platforms for generating more accurate data for drug screening and predicting treatment outcomes.

This Research Topic presents a comprehensive review of biomechanical changes and their pharmacological implications, exploring variations in drug action and the mechanisms underlying these effects in relation to biomechanical elements.

Recognizing the growing importance of biomechanics and pharmacology, we invite submissions of various article types, including original research, review papers, methodology articles, and other relevant publications.

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Frontiers in Pharmacology

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