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Nanoparticles Interacting with Membranes: From Engulfment Patterns to Endocytosis
Monday, February 29, 2016 circularity, and final dumbbell morphology. Seeds corresponding to dividing cells were split into two equidistant seeds along the longest cell axis. We found that 84.354.0% of anterior cells immediately adjacent to the ventral midline (ventral cells) divided within 45 of the AP axis. In contrast, anterior cells away from the midline (lateral cells) divided at random orientations. Cell shape analysis revealed that ventral cells rotated 32.553.0 before cell division to align their longest axis with the AP axis, while lateral cells did not undergo a similar rotation. Together, our data strongly suggest that the mechanisms that promote oriented cell division are spatially regulated. 942-Plat Agent-Based Modeling of Biological Pathways - A Case-Study on mRNA Export and Quality Control Mechanism Mohammad Soheilypour, Mohammad Mofrad. University of California, Berkeley, Berkeley, CA, USA. Currently, a substantial gap exists between the methods utilized for modeling biological pathways. While some methods rely heavily on assumptions that prevent them from capturing the spatial detail and stochastic behavior observed in nature, others are designed to account for deeper levels of spatial details and stochasticity but at the cost of increased computational time and resources. Agent-based modeling (ABM) is a highly promising approach that brings together the advantages of detailed spatiotemporal approaches and computationally inexpensive methods. ABMs consist of a collection of agents with governing rules that dictate local behavior and interactions with adjacent agents, eventually predicting the complex behavior that may not be obvious from the individual rules. Our recently developed ABM platform, called BioABM, is primarily designed to capture the dynamics of molecular-scale complex systems by associating diffusion and binding/unbinding constants of biological species to movement and interaction probabilities in ABM. In order to showcase its potential impact as a predictive tool, we apply BioABM to an important, yet not well understood, biological pathway, i.e. messenger ribonucleic acid (mRNA) export and quality control mechanism. mRNAs are transported to the cytoplasm to transfer genetic information and direct synthesis of functional proteins. Multiple proteins and complexes are involved and the process is meticulously quality controlled by various sophisticated, yet highly efficient, mechanisms in eukaryotic cells. Using BioABM, we explored the dynamics of mRNA export and the mechanism through which aberrant mRNAs are distinguished and retained inside the nucleus. Our results shed light on different aspects of this pathway; addressing factors such as the significance of the expression level of mRNA export factor and the length of mRNA as well as presence of a nuclear basket-associated quality control complex on mRNA export dynamics.
Platform: Membrane Physical Chemistry II 943-Plat Nanoparticles Interacting with Membranes: From Engulfment Patterns to Endocytosis Jaime Agudo-Canalejo, Reinhard Lipowsky. Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany. Nanoparticles are used to deliver drugs, imaging agents, and toxins to biological cells. The delivery requires the engulfment of the nanoparticles by cell membranes, a process that is governed by the interplay of particle adhesion and membrane bending and can be mimicked in model systems consisting of lipid or polymer vesicles. Previous theoretical studies of these systems have focussed on the engulfment of nanoparticles by planar membranes and symmetric bilayers. Here, we consider the general case of nanoparticles interacting with asymmetric bilayer membranes that form complex shapes with nonuniform curvature. Even small bilayer asymmetries lead to two critical particle sizes that determine four distinct engulfment regimes. [1] These regimes depend on two material parameters, the contact mean curvature and the spontaneous curvature, as well as on the local curvature of the membrane segments in contact with the nanoparticles. As a consequence, different segments of the same membrane can belong to different engulfment regimes and a single vesicle in contact with many nanoparticles can display ten distinct engulfment patterns as well as morphological transitions between these patterns. [2] In order to address the more complex process of receptor-mediated endocytosis, we extend our results to account for adhesion-induced segregation of the membrane components and increased spontaneous curvatures arising from protein coats. [1] We derive explicit expressions for the engulfment rate and total uptake of nanoparticles by cells, which are both predicted to depend nonmonotonically on the particle size. These expressions provide a quantitative fit to experimental data for the size-dependence of clathrin-dependent endocytosis of gold nanoparticles by HeLa cells.
189a
[1] J. Agudo-Canalejo and R. Lipowsky. ACS Nano 9, 3704 (2015) [2] J. Agudo-Canalejo and R. Lipowsky. Nano Letters (in press) 944-Plat On the Formation of Lipid Nano-Scale Structures at Interfaces Beyond Planar Bilayers Aleksandra Dabkowska1, Cassandra Niman2, Gaelle Offranc Piret3, Henrik Persson4, Hanna Wacklin5, Heiner Linke6, Christelle Prinz6, Tommy Nylander1. 1 Physical Chemistry, Lund University, Lund, Sweden, 2Division of Solid State Physics, Lund University, Lund, Sweden, 3Biomedical Research Center Edmond J. Safra, Clinatec Laboratory, Grenoble, France, 4Experimental Medical Science, Lund University, Lund, Sweden, 5European Spallation Source ESS, Lund, Sweden, 6Solid State Physics, Lund University, Lund, Sweden. Biological membranes do not only occur as planar bilayer structures, but bilayers have also been shown to, depending on the lipid composition, curve into intriguing 3D structures. Understanding the biological implication as well as the application of such interfaces, for e.g. drug delivery and other biomedical application, requires the development of well-defined model system. Here we demonstrate the formation of fluid supported bilayers on vertical gallium phosphide nanowire (NW) forests using self-assembly from lipid vesicular dispersions (1-2). The phospholipid mixture used had a composition that facilitates the formation of curved bilayers. By applying fluorescence recovery after photobleaching, we determined that the lipids are able to diffuse laterally within the NW-supported bilayer and that the bilayers were found to follow the contours of the nanowires to form continuous and locally highly curved model membranes. Membrane-anchoring proteins as well as tethered vesicles were found to be able to bind to these bilayers on the nanowire substrate. (1) Dabkowska, A.P., Niman, C.S., Piret, G., Persson, H., Wacklin, H.P., Linke, H., Prinz, C.N. & Nylander, T. Fluid and highly curved model membranes on vertical nanowire arrays. Nano Letters, 2014, 14, 4286-4292. (2) Dabkowska, A. P., Piret, G., Niman, C. S., Lard, M., Linke, H., Nylander, T., Prinz, C., N.: Surface nanostructures for fluorescence probing of supported lipid bilayers on reflective substrates. 2015, Accepted in Nanoscale 945-Plat a-Synuclein Bound to Mitochondrial Membranes—Changes in Lipid Bilayer Structure and Mechanics Ana West, Ben Brummel, Jonathan Sachs. Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA. The association between a-Synuclein and mitochondrial membranes is believed to be an important event in the neuronal degeneration that leads to Parkinson Disease (PD). In particular,a-Synuclein binding to mitochondrial membranes has recently been seen to cause organelle fragmentation and suppression of mitochondrial fusion. The partitioning of monomeric a-Synuclein in the lipid bilayer and subsequent bilayer remodeling has been previously described for simple, model lipid bilayers that lack the complexity of mitochondrial membranes. Here, we ran a series of coarse-grain molecular dynamics MARTINI simulations of a-Synuclein absorbed in either pure cardiolipin bilayers or in mixed lipid bilayers that reflect the lipid composition of inner mitochondrial membrane of rat brain mitochondria. We investigated changes in bilayer structure and variations in lipid solvation near a-synuclein. A thinning of the bilayer is observed in simulations having higher levels of added protein. Other aspects studied include a-Synuclein partition depth (investigated by potential of mean force calculations), bilayer bending rigidities and curvature as a function of protein and/or cardiolipin density. 946-Plat Membrane Fluctuations Effect Protein Diffusion and Induce Protein Aggregation Kayla Sapp, Lutz Maibaum. Chemistry, University of Washington, Seattle, WA, USA. When proteins bind to cellular membranes the physical properties of both components are altered in unexpected and biologically relevant ways. We study a system of scaffolding proteins on the membrane, which locally impose a specific curvature on the membrane. We propose a generic model that takes into consideration the membrane’s elastic behavior, the steric repulsion between proteins, and the induced curvature of the membrane due to the proteins’ intrinsic curvature. Using analytical methods and stochastic computer simulations, we show that within this model the membrane mediates an attractive interaction between proteins. Furthermore, the projected protein diffusion is altered due to the curvature-coupling between the membrane and proteins. Our results illustrate the importance of membrane-induced effects on the spatial organization and dynamics of membrane-bound proteins.
Platform: Membrane Physical Chemistry II 943-Plat Nanoparticles Interacting with Membranes: From Engulfment Patterns to Endocytosis Jaime Agudo-Canalejo, Reinhard Lipowsky. Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany. Nanoparticles are used to deliver drugs, imaging agents, and toxins to biological cells. The delivery requires the engulfment of the nanoparticles by cell membranes, a process that is governed by the interplay of particle adhesion and membrane bending and can be mimicked in model systems consisting of lipid or polymer vesicles. Previous theoretical studies of these systems have focussed on the engulfment of nanoparticles by planar membranes and symmetric bilayers. Here, we consider the general case of nanoparticles interacting with asymmetric bilayer membranes that form complex shapes with nonuniform curvature. Even small bilayer asymmetries lead to two critical particle sizes that determine four distinct engulfment regimes. [1] These regimes depend on two material parameters, the contact mean curvature and the spontaneous curvature, as well as on the local curvature of the membrane segments in contact with the nanoparticles. As a consequence, different segments of the same membrane can belong to different engulfment regimes and a single vesicle in contact with many nanoparticles can display ten distinct engulfment patterns as well as morphological transitions between these patterns. [2] In order to address the more complex process of receptor-mediated endocytosis, we extend our results to account for adhesion-induced segregation of the membrane components and increased spontaneous curvatures arising from protein coats. [1] We derive explicit expressions for the engulfment rate and total uptake of nanoparticles by cells, which are both predicted to depend nonmonotonically on the particle size. These expressions provide a quantitative fit to experimental data for the size-dependence of clathrin-dependent endocytosis of gold nanoparticles by HeLa cells.
189a
[1] J. Agudo-Canalejo and R. Lipowsky. ACS Nano 9, 3704 (2015) [2] J. Agudo-Canalejo and R. Lipowsky. Nano Letters (in press) 944-Plat On the Formation of Lipid Nano-Scale Structures at Interfaces Beyond Planar Bilayers Aleksandra Dabkowska1, Cassandra Niman2, Gaelle Offranc Piret3, Henrik Persson4, Hanna Wacklin5, Heiner Linke6, Christelle Prinz6, Tommy Nylander1. 1 Physical Chemistry, Lund University, Lund, Sweden, 2Division of Solid State Physics, Lund University, Lund, Sweden, 3Biomedical Research Center Edmond J. Safra, Clinatec Laboratory, Grenoble, France, 4Experimental Medical Science, Lund University, Lund, Sweden, 5European Spallation Source ESS, Lund, Sweden, 6Solid State Physics, Lund University, Lund, Sweden. Biological membranes do not only occur as planar bilayer structures, but bilayers have also been shown to, depending on the lipid composition, curve into intriguing 3D structures. Understanding the biological implication as well as the application of such interfaces, for e.g. drug delivery and other biomedical application, requires the development of well-defined model system. Here we demonstrate the formation of fluid supported bilayers on vertical gallium phosphide nanowire (NW) forests using self-assembly from lipid vesicular dispersions (1-2). The phospholipid mixture used had a composition that facilitates the formation of curved bilayers. By applying fluorescence recovery after photobleaching, we determined that the lipids are able to diffuse laterally within the NW-supported bilayer and that the bilayers were found to follow the contours of the nanowires to form continuous and locally highly curved model membranes. Membrane-anchoring proteins as well as tethered vesicles were found to be able to bind to these bilayers on the nanowire substrate. (1) Dabkowska, A.P., Niman, C.S., Piret, G., Persson, H., Wacklin, H.P., Linke, H., Prinz, C.N. & Nylander, T. Fluid and highly curved model membranes on vertical nanowire arrays. Nano Letters, 2014, 14, 4286-4292. (2) Dabkowska, A. P., Piret, G., Niman, C. S., Lard, M., Linke, H., Nylander, T., Prinz, C., N.: Surface nanostructures for fluorescence probing of supported lipid bilayers on reflective substrates. 2015, Accepted in Nanoscale 945-Plat a-Synuclein Bound to Mitochondrial Membranes—Changes in Lipid Bilayer Structure and Mechanics Ana West, Ben Brummel, Jonathan Sachs. Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA. The association between a-Synuclein and mitochondrial membranes is believed to be an important event in the neuronal degeneration that leads to Parkinson Disease (PD). In particular,a-Synuclein binding to mitochondrial membranes has recently been seen to cause organelle fragmentation and suppression of mitochondrial fusion. The partitioning of monomeric a-Synuclein in the lipid bilayer and subsequent bilayer remodeling has been previously described for simple, model lipid bilayers that lack the complexity of mitochondrial membranes. Here, we ran a series of coarse-grain molecular dynamics MARTINI simulations of a-Synuclein absorbed in either pure cardiolipin bilayers or in mixed lipid bilayers that reflect the lipid composition of inner mitochondrial membrane of rat brain mitochondria. We investigated changes in bilayer structure and variations in lipid solvation near a-synuclein. A thinning of the bilayer is observed in simulations having higher levels of added protein. Other aspects studied include a-Synuclein partition depth (investigated by potential of mean force calculations), bilayer bending rigidities and curvature as a function of protein and/or cardiolipin density. 946-Plat Membrane Fluctuations Effect Protein Diffusion and Induce Protein Aggregation Kayla Sapp, Lutz Maibaum. Chemistry, University of Washington, Seattle, WA, USA. When proteins bind to cellular membranes the physical properties of both components are altered in unexpected and biologically relevant ways. We study a system of scaffolding proteins on the membrane, which locally impose a specific curvature on the membrane. We propose a generic model that takes into consideration the membrane’s elastic behavior, the steric repulsion between proteins, and the induced curvature of the membrane due to the proteins’ intrinsic curvature. Using analytical methods and stochastic computer simulations, we show that within this model the membrane mediates an attractive interaction between proteins. Furthermore, the projected protein diffusion is altered due to the curvature-coupling between the membrane and proteins. Our results illustrate the importance of membrane-induced effects on the spatial organization and dynamics of membrane-bound proteins.