Uterine motility is responsible for carrying out important processes throughout all phases of the female reproductive cycle, including sperm transport, menstruation, and embryo implantation. We present a model of intra-uterine fluid flow in a sagittal cross-section of the uterus by inducing peristalsis in a channel. The peristaltic waveform emerges from the coupling of cellular models to elastic walls and viscous fluid. This is an integrative multiscale spatial model that takes as input the fluid viscosity, passive uterine tissue properties, and a prescribed wave of membrane depolarization. Following Bursztyn et al. [1], the voltage pulse drives the calcium dynamics inside each smooth muscle cell along the uterine walls. This, in turn, drives the formation of cross-bridges in the cell which generate the contractile muscle forces. The forces predicted by this new model are coupled to the elastic channel walls and the viscous, incompressible fluid within the channel using an immersed boundary framework [2] The main contributions of this dissertation are two-fold. First, we present a modified Hai-Murphy model of uterine smooth muscle cell force generation that accounts for the displacement of myosin cross-bridge heads relative to their binding sites. Second, we couple this microscale model of force generation with an organ level model of the uterine channel that captures the elastic properties of the uterine walls and a viscous, incompressible fluid. We then examine how fluid transport is affected by changes on the molecular and cellular scales. In particular, we show how deficiencies in phosphorylation and calcium uptake affect intra-uterine fluid flow / acase@tulane.edu

<p> Individuals, post-stroke, present with an array of changes to the neuromuscular system function such as muscle weakness and abnormal muscle activation patterns. Different combinations of these and other altered body functions result in limitations in functional mobility, such as reduced gait speed and high risk for falls. In this series of studies, I developed a deeper understanding of how neuromechanical factors may limit the fastest speed that an individual post-stroke can reach before they are unable to move any faster without losing balance. I conducted three studies. In the first study, my results showed that, after stroke, individuals have the capacity to walk at faster speeds than their overground self-selected maximum walking speed, while walking on a treadmill and when provided horizontal assistance using a robotic device. In the second study, I showed that non-impaired individuals modulated the amplitude and phasing of muscle activity according to the requirements brought about by the existence of horizontal assistive forces during walking at progressively faster speeds. Finally, in the third study I showed that individuals post-stroke also were able to modulate amplitude and phasing of muscle activity in both legs, according to the requirements brought about by the existence of horizontal assistive forces during walking at progressively faster speeds. However, the paretic leg was more responsive to horizontal assistive forces than the non-paretic leg. The understanding gained through these studies provide novel insights regarding the capabilities of individuals with post-stroke hemiparesis to adapt their existing impaired neuromuscular mechanisms into more challenging walking tasks. Each study leads to ideas for the development of potentially more effective rehabilitation protocols targeted at the modulation of amplitude and phasing of muscle activity in order to safely achieve faster walking speeds. </p>

Glaucoma is the second leading cause of irreversible blindness in the world. It is characterized by the cupping of optic nerve head (ONH), loss of retinal ganglion cells and their axons resulting in loss of functional visual field. It is known that elevated intraocular pressure (IOP) is related to the disease, however the underlying pathophysiology of glaucoma in relation to IOP is not well understood and the factors contributing to disease progression are not well characterized The object of this work is to develop a three dimensional (3D) histomorphometry technique to study how the connective tissue and prelaminar neural tissue of the normal ONH respond to acute changes in IOP, and how these tissues response to long term IOP elevation in the early glaucoma (EG). The study of the ONH tissues is important because these tissues provide structural and nutritional support to the axons while they pass through the ONH. Furthermore, as the ONH is the primary site of axonal injury in glaucoma, investigation of its connective tissues provides may provide insight into the mechanism by which axons are damaged In this study, a 3D histomorphometry technique was introduced to reconstruct the ONH, delineate and quantify the major structures using customized software. Our major findings are: (1) Connective tissue and prelaminar neural tissue were permanently altered in EG. Lamina cribrosa permanently deformed in a posterior direction and thickened, accompanied by thickening of the prelaminar neural tissue. (2) The connective tissues deformed following acute IOP elevation characterized by thinning of the lamina, posterior bowing of the sclera and minimum anterior or posterior displacement of lamina. (3) Inter-eye physiologic differences of the normal ONH geometry were small enough to allow us to identify the effects of both acute and chronic IOP elevation to the ONH geometry. Finally new parameterized specimen-specific finite element models of the ONH and scleral shell were developed to study ONH biomechanics. Our study showed that the laminar elastic constant, scleral modulus, scleral thickness and laminar anisotropy were the most influential factors determining ONH biomechanics. In addition, the geometric and mechanical properties interacted to affect the ONH biomechanics / acase@tulane.edu

Zellmembranen sind hochspezialisierte Mehrkomponentenlegierungen, welche sowohl die Zelle selbst als auch ihre Organellen umgeben. Sie spielen eine entscheidende Rolle bei vielen biologisch relevanten Prozessen wie die Signaltransduktion und die Zellbewegung. Aus diesem Grund ist eine genaue Charakterisierung ihrer Eigenschaften der Schlüssel zum Verständnis der Bausteine des Lebens sowie ihrer Erkrankungen. Besonders Krebs steht im engen Zusammenhang mit Veränderungen der biomechanischen Eigenschaften vom Gewebe, Zellen und ihren Organellen. Während Veränderungen des Zytoskeletts von Krebszellen im Fokus vieler Biophysiker stehen, ist die Bedeutung der Biomechanik von Zellmembran weitgehend unklar. Zellmembranen faszinieren Wissenschaftler jedoch nicht nur wegen ihrer biomechanischen Eigenschaften. Sie sind auch Beispiele für eine selbstorganisierte und heterogene Landschaft, in der Prozesse fernab des Gleichgewichtes, wie z.B. räumliche und zeitliche Musterbildungen, auftreten. Die vorgelegte Dissertation untersucht erstmals umfassend die zentrale Rolle der Zellmembran und ihrer molekularen Architektur für die Signalübertragung, die Biomechanik und die Zellmigration. Hierfür werden einfache Modellmembranen aber auch komplexere Vesikel und ganze Zellen mittels etablierter physikalischer Methoden analysiert. Diese reichen von Fourier- Analysen zur Charakterisierung von thermisch angeregten Membranundulationen über Massenspektrometrie und ‘Optical Stretcher’ Messungen von ganzen Zellen bis hin zur Filmwaagentechnik. Des Weiteren wird ein Modellsystem vorgestellt, welches sowohl einen experimentellen als auch einen mathematischen Zugang zum ‘ME-switch’ ermöglicht. Die vorgelegte Dissertation bietet neue Einblicke in wichtige Funktionen von Zellmembranen und zeigt neue therapeutische Perspektiven in der Membran- und Krebsforschung auf.:1 Introduction 2 Background 2.1 The Cell Membrane 2.1.1 Lipids in Cell Membranes 2.1.2 Membrane Proteins 2.1.3 An Overview on Membrane Models 2.1.4 Lipid Rafts 2.2 Model Membranes – An Experimental Access to Cell Membranes 2.2.1 Surface Tension and Thermodynamic Equilibrium 2.2.2 Langmuir Monolayer 2.2.3 The Polymorphism of Langmuir Monolayers 2.2.4 Membrane Vesicles 2.3 Biological Membranes as Semiflexible Shells 2.3.1 Elasticity of Soft Shells 2.3.2 Helfrichs Theory About Bending Deformations 2.3.3 Membrane Undulation 2.4 Membranes in Cell Signaling 2.4.1 Signal Transduction Fundamentals 2.4.2 Phosphoinositides 2.4.3 Phosphatidylinositol Signaling Pathway 2.4.4 The Myristoyl-Electrostatic Switch 2.5 Reaction-Diffusion Systems 2.5.1 Diffusion 2.5.2 Michaelis-Menten Kinetics 2.5.3 Reaction-Diffusion Systems 3 Methods, Materials and Theory 3.1 Optical Microscopy 3.1.1 Fluorescence Microscopy 3.1.2 Phase Contrast Microscopy 3.2 Cell Culture and GPMV Formation 3.2.1 Tumor Dissociation and Cell Culturing of Primary Cells 3.2.2 Cell Lines and Cell Culturing 3.2.3 Preparation of Giant Plasma Membrane Vesicles 3.3 Optical Stretcher 3.4 Fourier Analysis of Thermally Excited Membrane Fluctuations 3.4.1 The Quasi-Spherical Model – Membrane Fluctuations 3.4.2 Determination of the Bending Rigidity 3.5 Mass Spectrometry 3.5.1 MALDI-TOF Mass Spectrometry 3.5.2 ESI Mass Spectrometry 3.6 Migration, Invasion and Cell Death Assays 3.7 Langmuir-Blodgett Technique 3.7.1 Langmuir Troughs and Film Balances 3.7.2 Experimental Setup and Monolayer Preperation 3.7.3 Phospholipids, Dyes and Buffer Solutions 4 Fluctuations in Cell Membranes 4.1 Cell Membrane Softening in Human Breast and Cervical Cancer Cells 4.1.1 Bending Rigidity of Human Beast and Cervical Cell Membranes 4.1.2 MALDI-TOF Analysis of Lipid Composition 4.1.3 Summary and Discussion 4.2 Targeting of Membrane Rigidity – Implications on Migration 4.2.1 ESI Tandem Analysis of Lipid Composition 4.2.2 Biomechanical Behavior of Whole Cells and Membranes 4.2.3 Migration and Invasion Behavior 4.2.4 Summary and Discussion 5 Oscillations in Cell Membranes 5.1 Mimicking the ME-switch 5.1.1 DPPC/PIP2 monolayers at the presence of MARCKS 5.1.2 Lateral organization of PIP2 in DPPC/PIP2 monolayers 5.1.3 Translocation of MARCKS 5.1.4 Phosphorylation of MARCKS by PKC 5.1.5 Summary and Discussion 5.2 Dynamic Membrane Structure Induces Temporal Pattern Formation 5.2.1 Mechanism of the Oscillation 5.2.2 Modeling the ME-switch 5.2.3 Time Evolution 5.2.4 Phase Diagrams and Open Systems 5.2.5 Summary and Discussion 6 Conclusion and Outlook Appendix Bibliography List of Figures List of Abbreviations Acknowledgement