Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites

Area of Science:

• Biomaterials Science
• Cell Biology
• Biophysics

Background:

• Extracellular matrix (ECM) fibers, such as fibronectin (Fn), are crucial for tissue structure and cellular interactions.
• Unlike stiff materials, soft ECM fibers require unique mechanisms for deformation and rupture.
• Understanding Fn fiber mechanics is key to comprehending tissue remodeling and mechanotransduction.

Purpose of the Study:

• To investigate the extraordinary extensibility and mechanical properties of fibronectin (Fn) fibers.
• To elucidate the molecular mechanisms underlying Fn fiber deformation and recovery.
• To correlate Fn fiber mechanics with cellular responses and ECM remodeling.

Main Methods:

• Mechanical tensile testing of single Fn fibers to determine stress-strain relationships and Young's modulus.
• Analysis of hydrogen bond dynamics during stretching and relaxation using biophysical techniques.
• Utilizing intramolecular fluorescence resonance energy transfer (FRET) as a mechanical strain sensor in native ECM.

Main Results:

• Fn fibers demonstrate over 700% strain capacity, significantly exceeding typical biomaterials.
• Reversible breakage of force-bearing hydrogen bonds facilitates large reversible strains, unlike plastic deformation.
• Fiber extension increases rigidity and exposes cryptic binding sites, modulating cell behavior.
• Contraction kinetics involve rapid domain collapse followed by slower hydrogen bond network reestablishment.

Conclusions:

• Fibronectin fiber extensibility is a critical, tunable property of the extracellular matrix.
• The reversible rupture of hydrogen bonds is a novel mechanism for achieving high strain biomaterials.
• Mechanisms of Fn fiber deformation directly influence cell behavior and tissue remodeling.
• FRET-based sensors provide a method to study ECM mechanics in native environments.