The relative contributions of propulsive forces and receptor-ligand binding forces during early contact between spermatozoa and zona pellucida of oocytes

When reaching the zona pellucida (ZP) of the oocyte, spermatozoa apply propulsive forces produced by the motion of their flagella, which push against the ZP and theoretically should contribute to their penetration into the ZP. Additionally, specific receptors on the spermatozoon head bind to ZP3 ligands located on the surface of the ZP, which locks the sperm's head onto the oocyte. Both mechanisms are important cofactors in the initial sperm penetration into the ZP, which is required for successful fertilization of the oocyte, but it is unclear which forces-mechanical thrust or biochemical binding-are more influential at this stage. To address this question, we developed a biomechanical sperm-oocyte contact model, which is based on the Johnson-Kendall-Roberts model adopted from the contact mechanics theory. The modeling predicted that during the early stage of penetration into the ZP, biochemical binding forces acting on spermatozoa, which are swimming at a (normal) velocity of 100μm/s are ~4.2-times to ~16.7-times less than the mechanically-generated propulsive forces. In a simulated pathology of a low number of properly functioning receptors (50 out of 300receptors/μm ²), the biochemical binding forces are ~63-times less than the propulsive forces for the normally swimming sperm. It is suggested that such dominance of the propulsive forces over the biochemical binding forces can prevent efficient binding of spermatozoa to the ZP of the oocyte due to continuous movement of the sperm (which is not necessarily perpendicular to the ZP surface, and can cause sliding of sperm over the ZP). Thus, our theoretical analysis indicates that a sufficiently large density of receptors to ZP3 ligands on the sperm head is critical at the stage of early sperm-oocyte contact, in order to allow an efficient acrosome reaction to follow, so that the spermatozoon can start penetrating into the ZP.