Acyl-chain saturation regulates the order of phosphatidylinositol 4,5-bisphosphate nanodomains

Luís Borges-Araújo; Marco M Domingues; Alexander Fedorov; Nuno C Santos; Manuel N Melo; Fábio Fernandes

doi:10.1038/s42004-021-00603-1

Acyl-chain saturation regulates the order of phosphatidylinositol 4,5-bisphosphate nanodomains

Commun Chem. 2021 Nov 29;4(1):164. doi: 10.1038/s42004-021-00603-1.

Authors

Luís Borges-Araújo^{1

2}, Marco M Domingues³, Alexander Fedorov¹, Nuno C Santos³, Manuel N Melo², Fábio Fernandes^{4

5}

Affiliations

¹ Institute for Bioengineering and Biosciences (IBB) and Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
² Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.
³ Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
⁴ Institute for Bioengineering and Biosciences (IBB) and Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal. fernandesf@tecnico.ulisboa.pt.
⁵ Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisbon, Portugal. fernandesf@tecnico.ulisboa.pt.

Abstract

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) plays a critical role in the regulation of various plasma membrane processes and signaling pathways in eukaryotes. A significant amount of cellular resources are spent on maintaining the dominant 1-stearoyl-2-arachidonyl PI(4,5)P₂ acyl-chain composition, while less abundant and more saturated species become more prevalent in response to specific stimuli, stress or aging. Here, we report the impact of acyl-chain structure on the biophysical properties of cation-induced PI(4,5)P₂ nanodomains. PI(4,5)P₂ species with increasing levels of acyl-chain saturation cluster in progressively more ordered nanodomains, culminating in the formation of gel-like nanodomains for fully saturated species. The formation of these gel-like domains was largely abrogated in the presence of 1-stearoyl-2-arachidonyl PI(4,5)P_2. This is, to the best of our knowledge, the first report of the impact of PI(4,5)P₂ acyl-chain composition on cation-dependent nanodomain ordering, and provides important clues to the motives behind the enrichment of PI(4,5)P₂ with polyunsaturated acyl-chains. We also show how Ca²⁺-induced PI(4,5)P₂ nanodomains are able to generate local negative curvature, a phenomenon likely to play a role in membrane remodeling events.