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Engineering cellular response using nanopatterned bulk metallic glass.

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  • 1Center for Research on Interface Structures and Phenomena, Yale University , New Haven, Connecticut 06520, United States.

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Summary

Biomaterial nanopatterning engineers cell function. Bulk metallic glasses enable precise control, revealing how fibroblasts, macrophages, and endothelial cells detect feature sizes as small as 55 nm, influencing their morphology and behavior.

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Nanotechnology

Background:

  • Nanopatterning of biomaterials is a key strategy for controlling cell behavior.
  • Bulk metallic glasses (BMGs) offer versatile fabrication of nanopatterned surfaces for cell studies.

Purpose of the Study:

  • To investigate how different cell types detect and respond to various nanopattern feature sizes on BMG substrates.
  • To correlate cellular morphology and responses with substrate nanotopography and underlying biomechanical cues.

Main Methods:

  • Fabrication of nanopatterned BMG substrates using thermoplastic forming.
  • Culturing and observing fibroblasts, macrophages, and endothelial cells on substrates with varying feature sizes.
  • Utilizing nondimensional analysis, molecular pathway analysis, and nanoscale traction force microscopy (FIB-SEM) to characterize cellular responses and biomechanics.

Main Results:

  • Fibroblasts detected feature sizes down to 55 nm, decreasing cell area with increasing feature size.
  • Macrophages responded to 200 nm features, showing increased size and elongation; they did not respond to 150 nm or smaller.
  • Endothelial cells responded to 100 nm features or larger with decreased size and elongation.
  • Nanopatterns affected protein adsorption, substrate stiffness, focal adhesion density, and Rho-A GTPase activation, leading to restricted cell spreading and reduced collagen production in fibroblasts.

Conclusions:

  • Cellular detection of nanopatterns is cell-type specific and dependent on feature size.
  • Substrate nanotopography directly influences cellular biomechanics, cytoskeletal remodeling, and function.
  • Nanoscale topography can be engineered to precisely control cellular responses for biomaterial applications.