Heparin's solution structure determined by small‐angle neutron scattering

Heparin is a linear, anionic polysaccharide that is widely used as a clinical anticoagulant. Despite its discovery 100 years ago in 1916, the solution structure of heparin remains unknown. The solution shape of heparin has not previously been examined in water under a range of concentrations, and here is done so in D2O solution using small‐angle neutron scattering (SANS). Solutions of 10 kDa heparin—in the millimolar concentration range—were probed with SANS. Our results show that when sodium concentrations are equivalent to the polyelectrolyte's charge or up to a few hundred millimoles higher, the molecular structure of heparin is compact and the shape could be well modeled by a cylinder with a length three to four times its diameter. In the presence of molar concentrations of sodium, the molecule becomes extended to nearly its full length estimated from reported X‐ray measurements on stretched fibers. This stretched form is not found in the presence of molar concentrations of potassium ions. In this high‐potassium environment, the heparin molecules have the same shape as when its charges were mostly protonated at pD ≈ 0.5, that is, they are compact and approximately half the length of the extended molecules.