A General Approach for Generating Fluorescent Probes to Visualize Piconewton Forces at the Cell Surface

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Cellular mechanical forces and extracellular matrix (ECM) interactions are crucial for development and disease.
• Mapping the dynamics of these forces at the receptor-ligand level is challenging.

Purpose of the Study:

• To develop a synthetic strategy for creating modular tension probes.
• To enable spatial and temporal mapping of molecular tension in living cells.

Main Methods:

• Combined native chemical ligation (NCL) with solid-phase peptide synthesis (SPPS).
• Generated a library of tension probes with diverse ligands, linkers, and reporters.
• Utilized probes for integrin and cadherin tension mapping.

Main Results:

• Demonstrated a novel synthetic approach for modular tension probes.
• Successfully mapped integrin and cadherin tension.
• Achieved the first long-term (approximately 3 days) molecular tension imaging.

Conclusions:

• The developed tension probes offer a versatile toolset for studying mechanotransduction.
• This method advances the ability to visualize and understand cell-matrix mechanical interactions.
• Provides insights into fundamental cell biology and disease processes like tumor progression.