Colloids and Surfaces A: Physicochemical and Engineering Aspects 208 (2002) 41 – 50 Adsorption of charged macromolecules on mixed fluid membranes Daniel Harries a , Sylvio May b , Avinoam Ben-Shaul a, * a Department of Physical Chemistry and the Fritz Haber Research Center, The Hebrew Uniersity, Jerusalem 91904, Israel b Institut fu ¨r Molekularbiologie, Friedrich -Schiller -Uniersita ¨t Jena, Winzerlaer Strasse 10, Jena 07745, Germany Received 11 June 2001; accepted 19 November 2001 Abstract The adsorption of charge rigid macromolecules, such as proteins from solution, on mixed (charged and neutral) lipid membranes is affected by several important factors. First, the mobile lipids in the membrane may rearrange, and demix locally to match the charge density of the apposed macromolecule, thus lowering the adsorption free energy. On the other hand, the (electrostatic) interaction between adsorbed macromolecules tends to lower the saturation coverage of the membrane. Additional factors, such as non-ideal lipid demixing or an elastic membrane response, enhanced by the presence of the charged macromolecules, may be at the base of the experimentally observed formation of high density protein domains and lateral macro-phase separation in lipid membranes. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Macromolecules; Electrostatic interactions; Lipid membranes www.elsevier.com/locate/colsurfa 1. Introduction Charge is carried by many biological molecules such as proteins, polynucleotides (e.g. DNA) and lipid membranes. The electrostatic interaction be- tween these macromolecules is at the base of many biological processes, such as protein – DNA binding, the adsorption of peripheral proteins onto cell membranes and the condensation of DNA in cell nuclei or viral capsids. Particular experimental and theoretical effort has been in- vested in the study of the adsorption of proteins onto charged lipid membranes since many biolog- ical processes, e.g. membrane activated enzymatic and signal transduction activity, occur at the membrane surface. This adsorption is also a pri- mary step in other processes such as the forma- tion of ion channels in cell membranes by self-assembled amphipathic peptides. A large number of experimental studies based mainly on fluorescence labeling and NMR tech- niques reveal that the adsorption process may occur in several stages [1–14]. At first, the basic proteins bind to the mixed, acidic and neutral lipid membrane. The fluid nature of the lipid bilayer allows the lipid constituent which interact * Corresponding author. Tel.: +972-2-6585271; fax: +972- 2-6513742 E-mail address: abs@fh.huji.ac.il (A. Ben-Shaul). 0927-7757/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0927-7757(02)00100-0