Biomechanical Alterations and Their Pharmacological Implications

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About this Research Topic

Background

The role of biomechanics, alongside biological cues, in influencing cellular function has been extensively researched. Physical stimuli originating from the extracellular matrix—such as deformability, stiffness, contraction/stretch, and external pressures—operate within living organisms both spatially and temporally to regulate cellular behavior. Mechanotransduction is a process believed to involve force transmission through bound proteins, leading to conformational changes that impact cell signaling, gene expression, phenotype, and function.
The importance of biomechanics in pharmacological contexts is increasingly highlighted in scientific literature. We argue that drug testing can be significantly refined by employing cells that exhibit phenotypes under (patho)physiologically relevant conditions. This approach ensures that assays replicate the actual biomechanical environment of the target condition.

It is well-documented that cellular responses to pharmacological agents differ markedly under biomimetic mechanical stimulation as opposed to conventional static conditions. For example, previous studies have shown that kidney cells cultured under microfluidic conditions with fluid shear exhibit increased sensitivity to nephrotoxic drugs compared to static conditions. In peristalsis models, both colon cancer and non-cancer cells have demonstrated reduced nanoparticle uptake compared to non-peristalsis conditions, resulting in decreased tumor treatment efficacy. Additionally, research has found that matrix stiffening in 2D and 3D cultures can induce chemoresistance. Certain genes influenced by mechanical pressures are also linked to medication resistance. These findings underscore the need to consider biomechanical cues during the screening and evaluation of drugs or nanoparticles.

With advancements in biomaterials, microfabrication, and microfluidic technologies, next-generation techniques such as 3D organoid culture, 3D bioprinting, organ-on-a-chip, and organoid-on-a-chip aim to replicate the architecture, morphology, function, and biophysical cues of tissues. This effort emulates the cellular environment found in the body. The integration of biological and biomechanical methodologies offers significant benefits for pharmacological research, providing enhanced simulations of the in vivo drug environment and yielding more accurate gene expression profiles than traditional cell cultures. Consequently, these innovative methodologies hold promise as platforms for generating more precise data in drug screening and predicting treatment outcomes.
This research topic provides a comprehensive review of biomechanical changes and their pharmacological implications, exploring variations in drug action and the mechanisms that underpin these effects in the presence of biomechanical elements.

Recognizing the growing intersection between biomechanics and pharmacology, the topic editors welcome a range of article types, including original research, review articles, methodological papers, and other contributions.

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This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

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  • Editorial
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  • Hypothesis and Theory
  • Methods
  • Mini Review
  • Opinion
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Data Report
  • Editorial
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review
  • Opinion
  • Original Research
  • Perspective
  • Review
  • Systematic Review
  • Technology and Code

Keywords: Biomimetic Culture, ECM Stiffness, Drug Effects, Mechanobiology, Organoid, Organ-on-a-chip

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