Prothrombin activation on phospholipid membranes with positive electrostatic potential.

Area of Science:

• Biochemistry
• Hematology
• Membrane Biophysics

Background:

• Prothrombin conversion to thrombin is vital for hemostasis and is enhanced by phospholipids and calcium ions.
• Previous research suggested negatively charged phospholipid surfaces are essential for promoting blood coagulation.

Purpose of the Study:

• To investigate the role of surface charge and the phosphatidylserine (PS) amino group in prothrombin conversion.
• To determine if electrostatic forces are critical for coagulation factor binding to PS-containing membranes.

Main Methods:

• Incorporation of stearylamine into phosphatidylserine (PS) and phosphatidyl-beta-lactate (PLac) membranes to alter surface charge.
• Assay of procoagulant and prothrombin-converting activity of modified membranes.

Main Results:

• Positively charged PS membranes retained significant procoagulant activity, indicating minimal contribution of electrostatic forces to factor binding.
• Introduction of stearylamine inhibited prothrombin conversion in PLac membranes but not in PS membranes.
• PS-containing vesicles exhibited higher procoagulant activity than PLac vesicles, highlighting the importance of the PS amino group.

Conclusions:

• The amino group of phosphatidylserine plays a critical role in procoagulant activity, independent of membrane surface charge.
• Calcium ion complex formation between coagulation factors and PS molecules likely drives the association with procoagulant membranes.
• This mechanism explains the high procoagulant efficacy of PS-containing cell membranes.