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Title:On the role of anisotropy of membrane constituents on the elastic properties of highly curved lipid membranes
Authors:ID Perutkova, Šarka (Author)
ID Kralj, Samo (Comentor)
ID Kralj-Iglič, Veronika (Mentor) More about this mentor... New window
Files:.pdf DOK_Perutkova_Sarka_2017.pdf (12,09 MB)
MD5: 391234AE6FF8FDB4DA9C4F6EDD204B72
 
Language:English
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:FNM - Faculty of Natural Sciences and Mathematics
Abstract:The primary objective of the thesis covers in the theoretical study the role of anisotropic membrane components in the elasticity of highly curved biological membranes. To show the importance of anisotropy, we focused on one type of non-lamellar membrane self-assembly - the inverted hexagonal phase and the membrane tubular protrusions with attached proteins. These two structures represent excellent examples of highly curved structures in which the anisotropy of molecules or small domains plays an important role. In the first part of the thesis, we developed a theoretical model describing the stability of the inverted hexagonal phase, which considers lipid anisotropy and deviations from the circularity of the pivotal plane cross-section. We applied a wedge-like model of phospholipid molecules, in which the phospholipid molecule is described as a wedge, with the angle of the wedge increasing with temperature. However, we also took into account the average orientation of lipids by including the deviatoric bending energy contribution derived from statistical physics. Theoretical predictions of our model showed that a crosssection of the inverted hexagonal phase is an intermediate between a circle and a hexagon, and that it has lower energy than the circular cross-section. The results were in agreement with observations gathered by the small angle X-ray scattering. By comparing our results with the experiments, we predicted some values of the mean intrinsic curvature and the phospholipid chain stiffness. In the second part of the thesis, we developed a theoretical model, which describes the stabilisation of membrane nanotubes containing attached anisotropic flexible rod-like proteins. We derived the free energy of a vesicle with nanotube taking into account the rotational averaging of the anisotropic attached proteins. We also added the entropy contribution due to the non-homogeneous lateral distribution of proteins. Our theoretical results showed that rod-like attached proteins and membrane domains can stabilise the membrane tubular protrusions if we consider the protein/ domain anisotropy. Our results were also in agreement with experimental results in which isotropic membrane constituents were found on the tips of the nanotube or on the mother vesicle; however, the anisotropic membrane constituents were detected along the nanotubes. Our results showed that rod-like attached proteins and membrane domains can stabilise the membrane tubular protrusions if we consider the protein/domain anisotropy. The anisotropy of membrane constituents can lower the membrane free energy in regions of high curvature. The main aim of the thesis was to show that the anisotropy of membrane constituents can lower the membrane free energy in regions of high curvature and that the rotational averaging of anisotropic membrane components should be considered in the evaluation of the membrane free energy at highly curved membrane structures.
Keywords:Biomembranes, Lipid anisotropy, Inverted hexagonal phase, Rotational averaging, Rod-like proteins, Membrane nanotubes, Membrane protein sorting
Place of publishing:[Maribor
Publisher:Š. Perutková]
Year of publishing:2017
PID:20.500.12556/DKUM-64957 New window
UDC:577.352:576.314(043.3)
COBISS.SI-ID:23112200 New window
NUK URN:URN:SI:UM:DK:IPTKCJUK
Publication date in DKUM:25.05.2017
Views:2372
Downloads:109
Metadata:XML DC-XML DC-RDF
Categories:FNM
:
PERUTKOVA, Šarka, 2017, On the role of anisotropy of membrane constituents on the elastic properties of highly curved lipid membranes [online]. Doctoral dissertation. Maribor : Š. Perutková. [Accessed 28 March 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=64957
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Secondary language

Language:Slovenian
Title:Vloga anizotropije membranskih gradnikov na elastomehanske lastnosti močno ukrivljenih lipidnih membran
Abstract:Biološke membrane predstavljajo eno izmed najbolj pomembnih struktur v celicah. Sestavljene so iz različnih vrst proteinov, peptidov in ogljikovih hidratov, ki plavajo v lipidni dvojni plasti. Zelo pomembna lastnost lipidne membrane, ki vpliva na njene mehanizme, je elasticnost. Anizotropija je bila vključena v opis membrane preko upoštevanja deviatorja ukrivljenosti namesto Gaussove ukrivljenosti in kasneje tudi z vpeljavo orientacijskega reda anizotropnih komponent. Anizotropne komponente membrane imajo dve različni lastni/notranji ukrivljenosti. Stabilnost močno ukrivljenih struktur kot so na primer tubularne strukture, ki rastejo iz matičnega vezikla, membranske pore, membranske brsti in nelamelare faze, še niso popolnoma razložene, saj teorije, ki upoštevajo samo izotropne membranske komponente, ne zadostujejo. Doktorska disertacija je orientirana teoretično. V njej smo se potrudili pokazati, da lahko stabilnost močno ukrivljenih membranskih struktur razložimo s upoštevanjem anizotropije membranskih komponent. Za predmet naših raziskav smo izbrali dve strukturi: invertno heksagonalno lipidno fazo in dolge tanke membranske cevke lipidnih veziklov, ki predstavljata tipična primera močno ukrivljenih lipidnih membran. Prvi del doktorske disertacije se osredotoča na iskanje stabilnih oblik invertne heksagonalne faze in na vrednosti elastičnih parametrov v tej fazi (lastna ukrivljenost in natezna trdnost lipidnih verig) v odvisnosti od temperature. V ta namen smo vpeljali teoretični model, v katerem smo obravnavali lipidne molekule kot anizotropne klinaste delce, lipidne verige pa še dodatno kot prožne vzmeti. Upoštevali smo tudi da je presek invertne heksagonalne faze različen od popolnega kroga. Stabilne oblike smo določili z numerično minimizacijo proste energije lipidne membrane. Prosto energijo membrane invertne heksagonalne faze smo izpeljali na podlagi metod statistične fizike, kjer smo upoštevali možnost vertikalne rotacije anizotropnih fosfolipidnih molekul z vpeljavo povprečnega orientacijskega reda. Iz minimizacije proste energije invertne heksagonalne faze smo pridobili stabilne oblike preseka, ki so bili vmes med ostro heksagonalo in povsem okroglo obliko. Naše izračunane oblike so se zelo dobro ujemale z eksperimentalnim. Na podlagi primerjav naših izračunov z eksperimentalnimi rezultati smo določili možne vrednosti elastičnih parametrov lipidne membrane v invertni heksagonalni fazi. V drugem delu doktorske disertacije so nas zanimali mehanizmi stabilizacije tubularnih lipidnih struktur, ki rastejo iz lipidnih veziklov zaradi adhezije ukrivljenih paličastih proteinov. Te proteine smo obravnavali kot fleksibilne delce s podobno upogibno trdostjo kot je upogibna trdnost membrane, ko so močno vezani na površino membrane. Izpeljali smo teorijo, ki vsebuje elastično energijo membrane ter elastično energijo na površino membrane adheziranih anizotropnih proteinov in njihov entropijski prispevek. Izračunali smo prosto energijo ter razporeditev proteinov za razlicne premere membranskih cevk in razlicne lastne ukrivljenosti proteinov. Rezultate smo kvalitativno primerjali z že objavljenimi eksperimentalnimi rezultati na celicnih membranah in na veziklih. Z našimi teoretičnimi modeli smo pokazali, da so lahko zelo ukrivljene membranske strukture, kot je invertna hexagonalna faza ali tanke valjaste membranske strukture, stabilne zaradi anizotropije njihovih gradnikov (fosolipidi, proteini ali proteinske domene). Z upoštevanjem orientacijske entropije se prosta energija membrane z anizotropnimi delci bistveno zniža, zato se struktura mehansko stabilizira. Brez upoštevanja anizotropije delcev prosta energija v takih strukturah ne bi imela minimuma.
Keywords:Biomembrane, Anizotropija lipidov, Ukrivljenost membrane, Invertna heksagonalna faza, Orentacijsko povprečje, Paličasti proteini, Membranske nanocevke, Porazdelitev membranskih proteinov


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