Controlling Protein Enrichment in Lipid Sponge Phase Droplets using SNAP‐Tag Bioconjugation

Abstract

All cells use organized lipid compartments to facilitate specific biological functions. Membrane‐bound organelles create defined spatial environments that favor unique chemical reactions while isolating incompatible biological processes. Despite the fundamental role of cellular organelles, there is a scarcity of methods for preparing functional artificial lipid‐based compartments. Here, we demonstrate a robust bioconjugation system for sequestering proteins into zwitterionic lipid sponge phase droplets. Incorporation of benzylguanine (BG)‐modified phospholipids that form stable covalent linkages with an O6‐methylguanine DNA methyltransferase (SNAP‐tag) fusion protein enables programmable control of protein capture. We show that this methodology can be used to anchor hydrophilic proteins at the lipid‐aqueous interface, concentrating them within an accessible but protected chemical environment. SNAP‐tag technology enables the integration of proteins that regulate complex biological functions in lipid sponge phase droplets, and should facilitate the development of advanced lipid‐based artificial organelles.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 19, 2022
Source ID
10.1002/cbic.202100624

Entities

People

  • Alessandro Fracassi
  • M Salvador Castell
  • Madison Edwards
  • Mahta Moinpour
  • Neal Devaraj
  • Roberto Javier Brea
  • S. K. Sinha
  • Simpson Joseph
  • Soenke Seifert
  • Sudip Pandey

Organizations

  • Argonne National Laboratory
  • Stanford University
  • University of California, San Diego
  • Xunta de Galicia

Tags

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Nanocomposite Materials Science