Protein Misfolding in Lipid-Mimetic Environments

  • Vladimir N. UverskyEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 855)


Among various cellular factors contributing to protein misfolding and subsequent aggregation, membranes occupy a special position due to the two-way relations between the aggregating proteins and cell membranes. On one hand, the unstable, toxic pre-fibrillar aggregates may interact with cell membranes, impairing their functions, altering ion distribution across the membranes, and possibly forming non-specific membrane pores. On the other hand, membranes, too, can modify structures of many proteins and affect the misfolding and aggregation of amyloidogenic proteins. The effects of membranes on protein structure and aggregation can be described in terms of the “membrane field” that takes into account both the negative electrostatic potential of the membrane surface and the local decrease in the dielectric constant. Water-alcohol (or other organic solvent) mixtures at moderately low pH are used as model systems to study the joint action of the local decrease of pH and dielectric constant near the membrane surface on the structure and aggregation of proteins. This chapter describes general mechanisms of structural changes of proteins in such model environments and provides examples of various proteins aggregating in the “membrane field” or in lipid-mimetic environments.


Membrane field Lipid mimetic Intrinsically disordered protein Protein misfolding Protein aggregation Protein-membrane interaction 




Atomic force microscopy


Anilino-8-napthalene sulfonate


Circular dichroism


Dimyristoyl phosphatidylcholine


1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] sodium salt


Dimyristoyl phosphatidylserine




Fourier transform infrared spectroscopy




Human serum albumin


Islet amyloid polypeptide


Intrinsically disordered protein


Intrinsically disordered protein region


Large unilamellar vesicle




Newt acidic fibroblast growth factor








1,2- dipalmitoyl-sn-glycero-3-phospho-RAC-(1-glycerol)








Small unilamellar vesicle




Thioflavin T



This work was supported in part by a grant from Russian Science Foundation RSCF № 14-24-00131


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of MedicineUniversity of South FloridaTampaUSA
  2. 2.Biology Department, Faculty of ScienceKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  3. 3.Institute for Biological InstrumentationRussian Academy of SciencesPushchinoRussia
  4. 4.Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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