Mechanochemical interactions in cancer cells - The role of substrate stiffness in cell behavior and drug response

Sep 22, 2026

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Cancer cells adhere to the extracellular matrix, sensing substrate stiffness and using mechanical cues to shape proliferation and invasive potential. While many studies address cell activity under mechanical or chemical factors separately, evidence on combined mechanical–chemical effects across metastatic stages is limited. In addition, how chemotherapeutic drugs act in relation to distinct cellular properties remains insufficiently explored. This study uses polyacrylamide gels with tunable elastic moduli to model host tissue environments for prostate cancer cells.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Abstract

Introduction

Prostate cancer context and heterogeneity

Actin cytoskeleton and mechanosignaling

ECM proteins, integrins, and elastic modulus

Prior studies on substrate rigidity

OPEN ACCESS Citation: Ramezani SR, Mojra A, TafazzoliShadpour M (2026) Mechanochemical interactions in cancer cells: The role of substrate stiffness in cell behavior and drug response. PLoS One 21(1): e0327874. [https://](https://)[ ](https://)[doi.org/10.1371/journal.pone.0327874](doi.org/10.1371/journal.pone.0327874) Editor: Ahmed El-Fiqi, Advanced Materials Technology Research Institute, National Research Centre, EGYPT Received: March 13, 2025 Accepted: June 16, 2025 Published: January 7, 2026 Copyright: © 2026 Ramezani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: All relevant data are included within the paper. Funding: The author(s) received no specific funding for this work. RESEARCH ARTICLE Mechanochemical interactions in cancer cells: The role of substrate stiffness in cell behavior and drug response Sayed Reza Ramezani1, Afsaneh Mojra1*, Mohammad Tafazzoli-Shadpour2 1 Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran, 2 Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran * [afsanehmojra23@gmail.com](afsanehmojra23@gmail.com) Abstract Cancer cells adhere to the extracellular matrix, where they sense and respond to variations in substrate stiffness, influencing their proliferation and invasive potential. Numerous studies have examined the biological activities of cells in relation to mechanical forces; however, research addressing the combined effects of mechanical and chemical interactions on cancer cell behavior across different metastatic stages remains limited. Moreover, the influence of chemotherapeutic drugs in the context of specific cellular characteristics remains underexplored. Therefore, in this study, synthetic polyacrylamide gels with varying elastic moduli were utilized to effectively mimic the diversity of host tissue environments for prostate cancer cells. Additionally, cellular behavior of prostate cancer cells with differing metastatic potential—low (LNCaP), medium (DU145), and high (PC3)—was evaluated in response to anticancer drugs. Ultimately, effects of drug treatment were comprehensively examined using Docetaxel, Bicalutamide, and Abiraterone Acetate, which target distinct cellular components and activate diverse signaling pathways. The assessments were based on the analysis of actin filament content and organization, size of nucleus, and cellular elastic modulus. The results revealed that a soft substrate improves the medication efficacy, resulting in an enhanced cell death rate of 40–60% compared to 20–30% on a stiff substrate. Cells cultured on soft substrates exhibited lower phalloidin content (8–16%) compared to those on stiff substrates (18–32%) . Additionally, drug treatments influenced cell mechanics, with Docetaxel reducing the elastic modulus, while Bicalutamide induced an increase. Based on these findings, a treatment strategy aimed at enhancing therapeutic efficacy can be proposed. Introduction Prostate cancer (PCa) is the second most common cancer in men worldwide [ 1–3] . It shows significant molecular variability within and between tumor foci in individuals PLOS One | [https://doi.org/10.1371/journal.pone.0327874](https://doi.org/10.1371/journal.pone.0327874) January 7, 2026 1 / 28 Competing interests: The authors have declared that no competing interests exist. as well as across foci in different patients [4] . In contrast to most cancers, PCa exhibits few identifiable genetic drivers [5 ,6], which makes it difficult to determine the mechanisms guiding its initiation and spread [7] . The migration of cancer cells involves complex functional changes which contribute to their spread, invasion, and metastasis. The first functional change involves

FAQs

How does substrate stiffness affect cancer cell behavior in this research?

The study evaluates how prostate cancer cells respond to variations in substrate elastic modulus, linking mechanical sensing to changes in behavior and drug response.

Which prostate cancer cell lines were used to represent different metastatic potential?

Low, medium, and high metastatic potential were modeled with LNCaP, DU145, and PC3 cells, respectively.

How were anticancer drugs evaluated in relation to cellular mechanics?

Docetaxel, Bicalutamide, and Abiraterone Acetate were applied, and outcomes were assessed using actin filament organization, nucleus size, and the cellular elastic modulus.

Sep 22, 2026

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