@phdthesis{Kav2019,
  author    = {Kav, Batuhan},
  title     = {Membrane adhesion mediated via lipid-anchored saccharides},
  doi       = {10.25932/publishup-42879},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-428790},
  school      = {Universit{\"a}t Potsdam},
  pages     = {125},
  year      = {2019},
  abstract  = {Membrane adhesion is a fundamental biological process in which membranes are attached to neighboring membranes or surfaces. Membrane adhesion emerges from a complex interplay between the binding of membrane-anchored receptors/ligands and the membrane properties. In this work, we study membrane adhesion mediated by lipid-anchored saccharides using microsecond-long full-atomistic molecular dynamics simulations. Motivated by neutron scattering experiments on membrane adhesion via lipid-anchored saccharides, we investigate the role of LeX, Lac1, and Lac2 saccharides and membrane fluctuations in membrane adhesion. We study the binding of saccharides in three different systems: for saccharides in water, for saccharides anchored to essentially planar membranes at fixed separations, and for saccharides anchored to apposing fluctuating membranes. Our simulations of two saccharides in water indicate that the saccharides engage in weak interactions to form dimers. We find that the binding occurs in a continuum of bound states instead of a certain number of well-defined bound structures, which we term as "diffuse binding". The binding of saccharides anchored to essentially planar membranes strongly depends on separation of the membranes, which is fixed in our simulation system. We show that the binding constants for trans-interactions of two lipid-anchored saccharides monotonically decrease with increasing separation. Saccharides anchored to the same membrane leaflet engage in cis-interactions with binding constants comparable to the trans-binding constants at the smallest membrane separations. The interplay of cis- and trans-binding can be investigated in simulation systems with many lipid-anchored saccharides. For Lac2, our simulation results indicate a positive cooperativity of trans- and cis-binding. In this cooperative binding the trans-binding constant is enhanced by the cis-interactions. For LeX, in contrast, we observe no cooperativity between trans- and cis-binding. In addition, we determine the forces generated by trans-binding of lipid-anchored saccharides in planar membranes from the binding-induced deviations of the lipid-anchors. We find that the forces acting on trans-bound saccharides increase with increasing membrane separation to values of the order of 10 pN. The binding of saccharides anchored to the fluctuating membranes results from an interplay between the binding properties of the lipid-anchored saccharides and membrane fluctuations. Our simulations, which have the same average separation of the membranes as obtained from the neutron scattering experiments, yield a binding constant larger than in planar membranes with the same separation. This result demonstrates that membrane fluctuations play an important role at average membrane separations which are seemingly too large for effective binding. We further show that the probability distribution of the local separation can be well approximated by a Gaussian distribution. We calculate the relative membrane roughness and show that our results are in good agreement with the roughness values reported from the neutron scattering experiments.},
  language  = {en}
}
@phdthesis{Latza2020,
  author    = {Latza, Victoria Maria},
  title     = {Interactions involving lipid-based surfaces},
  doi       = {10.25932/publishup-44559},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-445593},
  school      = {Universit{\"a}t Potsdam},
  pages     = {217},
  year      = {2020},
  abstract  = {Interactions involving biological interfaces such as lipid-based membranes are of paramount importance for all life processes. The same also applies to artificial interfaces to which biological matter is exposed, for example the surfaces of drug delivery systems or implants. This thesis deals with the two main types of interface interactions, namely (i) interactions between a single interface and the molecular components of the surrounding aqueous medium and (ii) interactions between two interfaces. Each type is investigated with regard to an important scientific problem in the fields of biotechnology and biology: 1.) The adsorption of proteins to surfaces functionalized with hydrophilic polymer brushes; a process of great biomedical relevance in context with harmful foreign-body-response to implants and drug delivery systems. 2.) The influence of glycolipids on the interaction between lipid membranes; a hitherto largely unexplored phenomenon with potentially great biological relevance. Both problems are addressed with the help of (quasi-)planar, lipid-based model surfaces in combination with x-ray and neutron scattering techniques which yield detailed structural insights into the interaction processes. Regarding the adsorption of proteins to brush-functionalized surfaces, the first scenario considered is the exposure of the surfaces to human blood serum containing a multitude of protein species. Significant blood protein adsorption was observed despite the functionalization, which is commonly believed to act as a protein repellent. The adsorption consists of two distinct modes, namely strong adsorption to the brush grafting surface and weak adsorption to the brush itself. The second aspect investigated was the fate of the brush-functionalized surfaces when exposed to aqueous media containing immune proteins (antibodies) against the brush polymer, an emerging problem in current biomedical applications. To this end, it was found that antibody binding cannot be prevented by variation of the brush grafting density or the polymer length. This result motivates the search for alternative, strictly non-antigenic brush chemistries. With respect to the influence of glycolipids on the interaction between lipid membranes, this thesis focused on the glycolipids' ability to crosslink and thereby to tightly attract adjacent membranes. This adherence is due to preferential saccharide-saccharide interactions occurring among the glycolipid headgroups. This phenomenon had previously been described for lipids with special oligo-saccharide motifs. Here, it was investigated how common this phenomenon is among glycolipids with a variety of more abundant saccharide-headgroups. It was found that glycolipid-induced membrane crosslinking is equally observed for some of these abundant glycolipid types, strongly suggesting that this under-explored phenomenon is potentially of great biological relevance.},
  language  = {en}
}