Matrix microarchitecture and myosin II determine adhesion in 3D matrices

Area of Science:

• Cell biology
• Biophysics
• Biomaterials science

Background:

• Cell adhesion in 3D matrices is poorly understood, leading to conflicting reports on adhesion size and morphology.
• Existing knowledge gaps hinder the development of effective tissue engineering strategies and understanding of tumor cell invasion.

Purpose of the Study:

• To systematically identify mechanisms governing cell adhesion in 3D matrices.
• To develop principles of 3D cell adhesion applicable to both 2D and 3D substrates.
• To resolve conflicting literature on 3D cell adhesion.

Main Methods:

• Investigated the role of nonmuscle myosin II activity in 3D cell adhesion.
• Assessed the impact of matrix stiffness and local fiber alignment on adhesion formation.
• Quantified adhesion size and morphology in response to varying microenvironmental cues.

Main Results:

• Nonmuscle myosin II activity is a key determinant of cell adhesion phenotype in 3D, similar to 2D.
• Decreased bulk matrix stiffness does not always inhibit elongated adhesion formation in 3D.
• Local matrix fiber orientation, independent of stiffness, modulates adhesive area and adhesion size.
• Cells form large adhesions in soft 3D matrices with aligned fibers.

Conclusions:

• 3D cell adhesion is regulated by myosin activity and the local microenvironment, specifically matrix architecture.
• Fiber orientation and diameter, in addition to stiffness, are critical parameters influencing adhesion.
• Findings clarify literature conflicts and highlight factors beyond stiffness in adhesion modulation.
• Principles have implications for tissue engineering and cancer cell invasion research.