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These extracellular structures are characteristic of Alzheimer\u2019s disease, the major cause of late-age dementia. The mechanisms of A\u03b2 plaque formation and deposition are far from being understood. A vast number of studies in the literature describe the efforts to analyze those mechanisms using a variety of tools. The present review focuses on biophysical studies mostly carried out with model membranes or with computational tools. This review starts by describing basic physical aspects of lipid phases and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of the biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The Methodological Section is followed by the core of the review, which includes a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort to understand A\u03b2-bilayer binding. Concepts such as A\u03b2 peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in A\u03b2\u2013membrane interaction are separately identified and discussed.<\/jats:p>","DOI":"10.3390\/ijms25126401","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T10:08:43Z","timestamp":1718014123000},"page":"6401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Understanding A\u03b2 Peptide Binding to Lipid Membranes: A Biophysical Perspective"],"prefix":"10.3390","volume":"25","author":[{"given":"Hasna","family":"Ahyayauch","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto Biofisika (CSIC, UPV\/EHU), Universidad del Pa\u00eds Vasco, 48940 Leioa, Spain"},{"name":"Institut Sup\u00e9rieur des Professions Infirmi\u00e8res et Techniques de Sant\u00e9, Rabat 60000, Morocco"},{"name":"Laboratoire de Biologie et Sant\u00e9, Unit\u00e9 Neurosciences, Neuroimmunologie et Comportement, Faculty of Sciences, Ibn Tofail University, K\u00e9nitra 14000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo E.","family":"Masserini","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-7470","authenticated-orcid":false,"given":"Alicia","family":"Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto Biofisika (CSIC, UPV\/EHU), Universidad del Pa\u00eds Vasco, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6270-9216","authenticated-orcid":false,"given":"F\u00e9lix M.","family":"Go\u00f1i","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto Biofisika (CSIC, UPV\/EHU), Universidad del Pa\u00eds Vasco, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1001\/jama.287.18.2335","article-title":"Alzheimer disease","volume":"287","author":"Cummings","year":"2002","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0006-291X(84)80190-4","article-title":"Alzheimer\u2019s disease: Initial report of the purification and characterization of a novel cerebro-vascular amyloid protein","volume":"120","author":"Glenner","year":"1984","journal-title":"Biochem. 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