Polymorphism of Biomembranes at the Nanoscale

In dieser Arbeit untersuchen wir den Polymorphismus von Biomembranen im Nanometerbereich anhand von Computermodellen. In Kapitel drei werden auf Dissipative Particle Dynamis basierende molekulare Simulationen genutzt, um die Wechselwirkungen zwischen Membranen und Nanotropfen mit hohen Oberflächenspannungen in der Größenordnung von Milli Newton pro Meter zu untersuchen. Wir zeigen, dass Nanotropfen eine negative Linienspannung an der dreiphasigen Kontaktlinie mit der Membran aufweisen. Die negative Linienspannung führt zu einem spontanen Symmetriebruch des Membran-Tropfensystems und zur Bildung eines enggeschlossenen länglichen Membranhalses. In Kapitel vier untersuchen wir Nanotropfen mit niedrigen Grenzflächenspannungen in der Größenordnung von Mikro-Newton pro Meter. Eine Energieminimierung ermöglicht uns, eine Vielzahl von Parametern zu variieren und die Abhängigkeit der Membranbenet-zungsphänomene von der Grenzflächenspannung, der Biegesteifigkeit, der Linienspannung und der spontanen Krümmung systematisch zu bestimmen. Wir beobachten eine neue morphologische Transformation, die sowohl die Vesikel als auch das Tröpfchen betrifft und eine weiter Geometrie mit gebrochener Rotationssymmetrie. Schließlich bestimmen wir die Grenze zwischen symmetrischen und asymmetrischen Kontaktlinien innerhalb des dreidimensionalen Parameterraums bei verschwindender spontanen Krümmung. In Kapitel fünf verwenden wir molekulare Simulationen, um die morphologischen Transformationen einzelner Nanovesikel mit unterschiedlichem Grad an Asymmetrie zwischen den beiden Schichten der Doppelmembranen zu beobachten. Wir beginnen mit kugelförmigen Vesikeln, die ein bestimmtes Wasservolumen einschließen und aus einer bestimmten Gesamtzahl von Lipiden bestehen. Wenn ihr Volumen verringert wird, verwandeln sich die kugelförmigen Vesikel in eine Vielzahl von nicht kugelförmigen Formen. Dieser Polymorphismus kann durch Umverteilung weniger Lipide zwischen der inneren und äußeren Schicht der Membranen kontrolliert werden.In this thesis, we use computational methods to study polymorphism of biomembranes at the nanoscales. In chapter three, we use molecular simulations based on dissipative particle dynamics to investigate the interaction of membranes with nanodroplets at high interfacial tensions of the order of milli Newton per meter. We find that nanodroplets have negative line tension at the three phase contact line on the membrane. The negative line tension leads to spontaneous symmetry breaking of the membrane-droplet system and formation of a tight-lipped membrane neck. In chapter four, we study nanodroplets with low interfacial tensions of the order of micro Newton per meter. We use energy minimization, which allows us to explore a wide range of parameters and to systemati-cally determine the dependence of membrane wetting phenomena on interfacial tension, bending rigidity, line tension, and spontaneous curvature. We observe a new morphological transformation that involves both vesicles and droplets, leads to another regime with broken rotational symmetry. Finally, we determine the boundary between symmetric and asymmetric contact line geometries within the three-dimensional parameter space in vanishing spontaneous curvature. In chapter five, we use molecular simulations to monitor the morphological transformations of individual nanovesicles with different degrees of asymmetry between the two leaflets of the bilayer membranes. We start with the assembly of spherical vesicles that enclose a certain volume of water and contain a certain total number of lipids. When we reduce their volume, the spherical vesicles transform into a multitude of nonspherical shapes such as oblates and stomatocytes as well as prolates and dumbbells. This polymorphism can be controlled by redistributing a small fraction of lipids between the inner and outer leaflets of the bilayer membranes. As a consequence, the inner and the outer leaflets experience different mechanical tensions

Mutual remodeling of interacting nanodroplets and vesicles

Biomolecular condensates are membrane-less organelles performing various functions inside cells which behaviour can be understood in terms of liquid-liquid phase separation and wetting. Here, the authors characterize the low interfacial tension regime of nanodroplets during endocytic and exocytic engulfment within an elastic membrane, study the role of the contact line symmetry, and show that nanodroplets and vesicles mutually remodel one anothe

Different pathways for engulfment and endocytosis of liquid droplets by nanovesicles

In this work, the authors investigate on how condensate droplets, arising from liquid-liquid phase separation, can be engulfed by nanovesicles via distinct pathways, leading to different vesicle-droplet morphologies. Two key parameters are the stress asymmetry of the vesicle membrane and the line tension of the contact line between vesicle and droplet

Is the Solution Activity Derivative Sufficient to Parametrize Ion–Ion Interactions? Ions for TIP5P Water

Biomolecular processes involve hydrated ions, and thus molecular simulations of such processes require accurate force-field parameters for these ions. In the best force-fields, both ion–water and anion–cation interactions are explicitly parametrized. First, the ion Lennard-Jones parameters are optimized to reproduce, for example, single ion solvation free energies; then ion-pair interactions are adjusted to match experimental activity or activity derivatives. Here, we apply this approach to derive optimized parameters for concentrated NaCl, KCl, MgCl₂, and CaCl₂ salt solutions, to be used with the TIP5P water model. These parameters are of interest because of a number of desirable properties of the TIP5P water model, especially for the simulation of carbohydrates. The results show, that this state of the art approach is insufficient, because the activity derivative often reaches a plateau near the target experimental value, for a wide range of parameter values. The plateau emerges from the interconversion between different types of ion pairs, so parameters leading to equally good agreement with the target solution activity or activity derivative yield very different solution structures. To resolve this indetermination, a second target property, such as the experimentally determined ion–ion coordination number, is required to uniquely determine anion–cation interactions. Simulations show that combining activity derivatives and coordination number as experimental target properties to parametrize ion–ion interactions, is a powerful method for reliable ion–water force field parametrization, and gives insight into the concentration of contact or solvent shared ion pairs in a wide range of salt concentrations. For the alkali and halide ions Li⁺, Rb⁺, Cs⁺, F^–, Br^–, and I^–, we present ion–water parameters appropriate at infinite dilution only

Cell-imprinted substrates act as an artificial niche for skin regeneration

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications

Cell-Imprinted Substrates Act as an Artificial Niche for Skin Regeneration

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly­(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications

Cell-Imprinted Substrates Act as an Artificial Niche for Skin Regeneration

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly­(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications

Cell-Imprinted Substrates Act as an Artificial Niche for Skin Regeneration

Bioinspired materials can mimic the stem cell environment and modulate stem cell differentiation and proliferation. In this study, biomimetic micro/nanoenvironments were fabricated by cell-imprinted substrates based on mature human keratinocyte morphological templates. The data obtained from atomic force microscopy and field emission scanning electron microscopy revealed that the keratinocyte-cell-imprinted poly­(dimethylsiloxane) casting procedure could imitate the surface morphology of the plasma membrane, ranging from the nanoscale to the macroscale, which may provide the required topographical cell fingerprints to induce differentiation. Gene expression levels of the genes analyzed (involucrin, collagen type I, and keratin 10) together with protein expression data showed that human adipose-derived stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape and characteristics of keratinocytes. The observed morphology of the ADSCs grown on the keratinocyte casts was noticeably different from that of stem cells cultivated on the stem-cell-imprinted substrates. Since the shape and geometry of the nucleus could potentially alter the gene expression, we used molecular dynamics to probe the effect of the confining geometry on the chain arrangement of simulated chromatin fibers in the nuclei. The results obtained suggested that induction of mature cell shapes onto stem cells can influence nucleus deformation of the stem cells followed by regulation of target genes. This might pave the way for a reliable, efficient, and cheap approach of controlling stem cell differentiation toward skin cells for wound healing applications