Three-Dimensional Collagen Topology Shapes Cell Morphology, beyond Stiffness.

Area of Science:

• Biomaterials Science
• Cell Biology
• Cancer Research

Background:

• Cellular heterogeneity is crucial in physiological and pathological processes like tumorigenesis.
• The extracellular matrix (ECM) significantly influences cellular heterogeneity.
• Developing accurate in vitro models requires replicating tissue characteristics that control cell fate.

Purpose of the Study:

• To fabricate a library of ECM models that mimic connective tissues and basement membranes.
• To investigate how independently controlled ECM properties affect cellular phenotype.
• To gain insights into cancer model engineering and drug testing.

Main Methods:

• Utilized electrospinning and drop casting biofabrication routes for ECM models.
• Varied protein composition, topology, and stiffness of ECM models.
• Employed electron microscopy, multiphoton imaging, and AFM nanoindentation for characterization.

Main Results:

• Successfully fabricated ECM models with tunable protein composition, topology, and stiffness.
• Demonstrated the ability to generate in vivo complexity of ovarian cancer cell phenotypes.
• Identified that 3D collagen fibril topology, not just composition or stiffness, patterns cell shape.

Conclusions:

• Developed advanced ECM models that recapitulate the dynamic cellular environment.
• Highlight the critical role of ECM topology in dictating cell morphology and potentially cancer progression.
• Provide a foundation for improved cancer model engineering and drug screening platforms.