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Here, using the evolutionarily unrelated \u03b1-helical and \u03b2-barrel membrane proteins from\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , we find that the hydrophobic thickness and the strength of amphiphile-amphiphile packing in amphiphilic assemblies are critical determinants of protein stability. Lipid solvation enhances protein stability by facilitating residue burial in the protein interior, reminiscent of the lipophobic effect. This lipid-mediated mechanism also strengthens the cooperative residue-interaction network, promoting the propagation of local structural perturbations throughout the protein. This study demonstrates the pivotal role of lipid solvation in modulating the stability of membrane proteins and their responses to external stimuli.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adv9568","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:59:13Z","timestamp":1751464753000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["The lipid bilayer strengthens the cooperative network of membrane proteins"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-1418","authenticated-orcid":true,"given":"Shaima","family":"MuhammedNazaar","sequence":"first","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-982X","authenticated-orcid":true,"given":"Matthew R.","family":"Necelis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-7421","authenticated-orcid":true,"given":"Yein C.","family":"Park","sequence":"additional","affiliation":[{"name":"Thomas C. 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