Low spring constant regulates P-selectin-PSGL-1 bond rupture

Area of Science:

• Biophysics
• Cellular Mechanics
• Immunology

Background:

• Selectin-ligand bond dissociation is vital for leukocyte recruitment, thrombosis, and metastasis.
• Understanding bond rupture at low loading rates (<10(2) pN/s) and low spring constants (k) is crucial but remains unclear.

Purpose of the Study:

• To quantify the forced dissociation of P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) bonds at low loading rates using an optical trap assay.
• To investigate the influence of low loading rates and low spring constants on bond rupture dynamics.

Main Methods:

• Utilized an optical trap assay to measure bond rupture forces.
• Coupled P-selectin and PSGL-1 onto glass microbeads.
• Quantified bond dissociation at loading rates up to 20 pN/s with low spring constants (approximately 10(-3)-10(-2) pN/nm).

Main Results:

• Bond rupture force remained similar as loading rate increased up to 20 pN/s.
• Bond rupture force varied with different combinations of spring constant (k) and velocity (v), even at the same loading rate.
• The most probable rupture force (f*) increased with the spring constant when k < 47.0 x 10(-3) pN/nm.

Conclusions:

• Bond dissociation at low loading rates is dependent on the spring constant.
• Bond rupture force is influenced by both the loading rate and the mechanical compliance of the force transducer.
• Provides new insights into P-selectin glycoprotein ligand 1 bond dissociation under low loading rate or low spring constant conditions.