1 research outputs found
Regulation of the Electric Charge in Phosphatidic Acid Domains
Although a minor component of the lipidome, phosphatidic
acid (PA)
plays a crucial role in nearly all signaling pathways involving cell
membranes, in part because of its variable electrical charge in response
to environmental conditions. To investigate how charge is regulated
in domains of PA, we applied surface-sensitive X-ray reflectivity
and fluorescence near-total-reflection techniques to determine the
binding of divalent ions (Ca<sup>2+</sup> at various pH values) to
1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphate (DMPA) and
to the simpler lipid dihexadecyl phosphate (DHDP) spread as monolayers
at the air/water interface. We found that the protonation state of
PA is controlled not only by the p<i>K</i><sub>a</sub> and
local pH but also by the strong affinity to PA driven by electrostatic
correlations from divalent ions and the cooperative effect of the
two dissociable protons, which dramatically enhance the surface charge.
A precise theoretical model is presented providing a general framework
to predict the protonation state of PA. Implications for recent experiments
on charge regulation by hydrogen bonding and the role of pH in PA
signaling are discussed in detail