Effect of matrix heterogeneity on cell mechanosensing

Area of Science:

• Biophysics
• Cell Biology
• Materials Science

Background:

• Cells perceive mechanical cues from the extracellular matrix (ECM), primarily stiffness.
• ECM stiffness is highly variable due to random fibrous structure and inclusions like vessels.
• It remains unclear if cellular stiffness sensing can overcome ECM heterogeneity.

Purpose of the Study:

• To investigate how ECM heterogeneity affects cellular sensing of local stiffness variations.
• To determine the length scales over which mechanical cues propagate through the ECM.

Main Methods:

• Combined experimental approaches with computational modeling.
• Quantified local stiffness variations at the cellular scale.
• Observed cell behavior using multicellular spheroids in heterogeneous matrices.

Main Results:

• Spatial heterogeneity in ECM stiffness at the cellular scale exceeded the stiffness increase from local stiff features.
• ECM heterogeneity was reduced at length scales larger than the average fiber length.
• Multicellular spheroids, larger than fiber length, preferentially spread towards stiff inclusions.

Conclusions:

• Single cells primarily sense the stiffness of immediately adjacent ECM fibers due to significant heterogeneity.
• Mechanical cue propagation through the ECM is length-scale dependent.
• Multicellular structures can integrate mechanical information over larger distances, sensing distant matrix features.