Molecular accessibility in relation to cell surface topography and compression against a flat substrate.

Area of Science:

• Biophysics
• Cell Biology
• Surface Science

Background:

• Cell recruitment and adhesion depend on molecular bonds between cells and substrates.
• Molecular localization on cell surface topography critically influences bonding and adhesion.
• Understanding molecular availability is key for designing cell-interactive devices and studying cellular processes.

Purpose of the Study:

• To develop a quantitative framework for assessing molecular availability at the cell-substrate interface.
• To incorporate cell surface deformability, interfacial forces, and topographical variations into the assessment.
• To predict how molecular availability changes with cell compression and to validate predictions using fluorescence microscopy.

Main Methods:

• Developed a theoretical framework to model molecular availability, accounting for cell deformability and surface protrusion variability.
• Analyzed the influence of molecular distribution preference (tip vs. base of protrusions) on availability.
• Integrated molecular distribution with evanescent wave decay for predicting fluorescence intensity in total internal reflectance fluorescence microscopy (TIR-FM).

Main Results:

• The framework quantitatively assesses molecular availability, considering cell deformability and surface topography.
• Model predictions accurately reflect how molecular availability changes with increasing cell compression.
• Predicted fluorescence intensities using the model showed strong agreement with experimental measurements on human neutrophils.

Conclusions:

• The developed framework provides a robust method for quantifying molecular availability at cell-substrate interfaces.
• This approach is valuable for understanding cell adhesion mechanisms and designing biomaterials.
• The study validates the framework's predictive power using TIR-FM experiments, highlighting its utility in biophysical research.