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A Novel Stretching Platform for Applications in Cell and Tissue Mechanobiology
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The role of capsule stiffness on cellular processing.

Huanli Sun1, Edgar H H Wong2, Yan Yan1

  • 1ARC Centre of Excellence in Convergent Bio-Nano Science and Technology , and the Department of Chemical and Biomolecular Engineering , The University of Melbourne , Parkville , Victoria 3010 , Australia .

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Summary

Particle stiffness influences how cells interact with and internalize polymer capsules. Softer hyaluronic acid (HA) capsules show increased cell uptake, offering insights for designing effective therapeutic carriers.

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Area of Science:

  • Biomaterials Science
  • Cellular Biology
  • Polymer Chemistry

Background:

  • Particle stiffness is a key factor in cell uptake dynamics.
  • Polymer capsules are promising as therapeutic carriers, but their biological behavior needs further understanding.
  • Controlling capsule stiffness is crucial for optimizing their use in medicine.

Purpose of the Study:

  • To prepare polysaccharide capsules with tunable stiffness using a novel method.
  • To investigate the impact of capsule stiffness on cellular interaction and intracellular distribution.
  • To provide design principles for polymer capsules in biomedical applications.

Main Methods:

  • Preparation of hyaluronic acid (HA) capsules via atom transfer radical polymerization-mediated continuous assembly of polymers (CAP$_{ATRP}$) on silica templates.
  • Systematic investigation of capsule-cell interactions using flow cytometry, imaging flow cytometry, and deconvolution microscopy.
  • Tuning capsule stiffness by controlling wall thickness.

Main Results:

  • Softer HA capsules (7.5 mN m-1) exhibited higher cell surface binding and cellular association compared to stiffer capsules (17.6-28.9 mN m-1).
  • Cellular internalization of HA capsules was dependent on stiffness, decreasing with increased stiffness.
  • Internalized capsules, regardless of stiffness, deformed and were localized in lysosomes.

Conclusions:

  • Capsule stiffness significantly influences cellular interaction, binding, and uptake.
  • The findings provide critical insights for the rational design of polymer capsules for targeted drug delivery and other biomedical applications.
  • Tunable stiffness in polysaccharide capsules offers a new avenue for optimizing therapeutic carrier performance.