Coupled effects of mechanics, geometry, and chemistry on bio-membrane behavior

Lipid bilayer membranes are models for cell membranes--the structure that helps regulate cell function. Cell membranes are heterogeneous, and the coupling between composition and shape gives rise to complex behaviors that are important to regulation. This thesis seeks to systematically build and analyze complete models to understand the behavior of multi-component membranes.

We propose a model and use it to derive the equilibrium and stability conditions for a general class of closed multi-component biological membranes. Our analysis shows that the critical modes of these membranes have high frequencies, unlike single-component vesicles, and their stability depends on system size, unlike in systems undergoing spinodal decomposition in flat space. An important implication is that small perturbations may nucleate localized but very large deformations. We compare these results with experimental observations.

We also study open membranes to gain insight into long tubular membranes that arise for example in nerve cells. We derive a complete system of equations for open membranes by using the principle of virtual work. Our linear stability analysis predicts that the tubular membranes tend to have coiling shapes if the tension is small, cylindrical shapes if the tension is moderate, and beading shapes if the tension is large. This is consistent with experimental observations reported in the literature in nerve fibers. Further, we provide numerical solutions to the fully nonlinear equilibrium equations in some problems, and show that the observed mode shapes are consistent with those suggested by linear stability. Our work also proves that beadings of nerve fibers can appear purely as a mechanical response of the membrane.

Establishing the C. elegans uterine seam cell (utse) as a novel model for studying cell behavior

The molecular inputs necessary for cell behavior are vital to our understanding of development and disease. Proper cell behavior is necessary for processes ranging from creating one’s face (neural crest migration) to spreading cancer from one tissue to another (invasive metastatic cancers). Identifying the genes and tissues involved in cell behavior not only increases our understanding of biology but also has the potential to create targeted therapies in diseases hallmarked by aberrant cell behavior.

A well-characterized model system is key to determining the molecular and spatial inputs necessary for cell behavior. In this work I present the C. elegans uterine seam cell (utse) as an ideal model for studying cell outgrowth and shape change. The utse is an H-shaped cell within the hermaphrodite uterus that functions in attaching the uterus to the body wall. Over L4 larval stage, the utse grows bidirectionally along the anterior-posterior axis, changing from an ellipsoidal shape to an elongated H-shape. Spatially, the utse requires the presence of the uterine toroid cells, sex muscles, and the anchor cell nucleus in order to properly grow outward. Several gene families are involved in utse development, including Trio, Nav, Rab GTPases, Arp2/3, as well as 54 other genes found from a candidate RNAi screen. The utse can be used as a model system for studying metastatic cancer. Meprin proteases are involved in promoting invasiveness of metastatic cancers and the meprin-likw genes nas-21, nas-22, and toh-1 act similarly within the utse. Studying nas-21 activity has also led to the discovery of novel upstream inhibitors and activators as well as targets of nas-21, some of which have been characterized to affect meprin activity. This illustrates that the utse can be used as an in vivo model for learning more about meprins, as well as various other proteins involved in metastasis.

Development of Microfluidic Devices with the Use of Nanotechnology to Aid in the Analysis of Biological Systems Including Membrane Protein Separation, Single Cell Analysis, and Genetic Markers

Computation technology has dramatically changed the world around us; you can hardly find an area where cell phones have not saturated the market, yet there is a significant lack of breakthroughs in the development to integrate the computer with biological environments. This is largely the result of the incompatibility of the materials used in both environments; biological environments and experiments tend to need aqueous environments. To help aid in these development chemists, engineers, physicists and biologists have begun to develop microfluidics to help bridge this divide. Unfortunately, the microfluidic devices required large external support equipment to run the device. This thesis presents a series of several microfluidic methods that can help integrate engineering and biology by exploiting nanotechnology to help push the field of microfluidics back to its intended purpose, small integrated biological and electrical devices. I demonstrate this goal by developing different methods and devices to (1) separate membrane bound proteins with the use of microfluidics, (2) use optical technology to make fiber optic cables into protein sensors, (3) generate new fluidic devices using semiconductor material to manipulate single cells, and (4) develop a new genetic microfluidic based diagnostic assay that works with current PCR methodology to provide faster and cheaper results. All of these methods and systems can be used as components to build a self-contained biomedical device.

Wave digital filter model of the entire auditory periphery

A model of the auditory periphery assembled from analog network submodels of all the relevant anatomical structures is described. There is bidirectional coupling between networks representing the outer ear, middle ear and cochlea. A simple voltage source representation of the outer hair cells provides level-dependent basilar membrane curves. The networks are translated into efficient computational modules by means of wave digital filtering. A feedback unit regulates the average firing rate at the output of an inner hair cell module via a simplified modelling of the dynamics of the descending paths to the peripheral ear. This leads to a digital model of the entire auditory periphery with applications to both speech and hearing research.

一篇探索真核细胞核起源的力作——读李靖炎先生的长篇近作“The primitive nucleus model and the origin of the cell nucleus”

《胞内共生与细胞研究》( 《Endocytobiosis and Cell Research》)是由国际胞内共生学会(International Society of Endocytobiology, ISE)主办的期刊, 它主要发表有关内共生物(endosy mbioses)和真核细胞的起源、发展、分化、进化和系统发育的研究论文. 在胞内共生和真核细胞的起源进化研究领域享有声誉. 去年该杂志发表了我国学者李靖炎先生的长篇论著“The primitive nucleus model and the origin of the cell nucleus(原始细胞核的模型与细胞核的起源)”(见1999, 13(1-3):1-86). 国外一家 SCI 收录的专业性刊物为中国学者发表一篇长达86页的 Review, 实不多见, 是我国学者在此领域的殊荣。

Cell types, network homeostasis, and pathological compensation from a biologically plausible ion channel expression model.

How do neurons develop, control, and maintain their electrical signaling properties in spite of ongoing protein turnover and perturbations to activity? From generic assumptions about the molecular biology underlying channel expression, we derive a simple model and show how it encodes an "activity set point" in single neurons. The model generates diverse self-regulating cell types and relates correlations in conductance expression observed in vivo to underlying channel expression rates. Synaptic as well as intrinsic conductances can be regulated to make a self-assembling central pattern generator network; thus, network-level homeostasis can emerge from cell-autonomous regulation rules. Finally, we demonstrate that the outcome of homeostatic regulation depends on the complement of ion channels expressed in cells: in some cases, loss of specific ion channels can be compensated; in others, the homeostatic mechanism itself causes pathological loss of function.

Evaluation of thermal radiation dependent performance of GaSb thermophotovoltaic cell based on an analytical absorption coefficient model

Applying the model dielectric function method, we have expressed the absorption coefficient of GaSb analytically at room temperature relating to the contribution of various critical points of its electronic band structure. The calculated absorption spectrum shows good agreement with the reported experimental data obtained by spectral ellipsometry on nominally undoped sample. Based on this analytical absorption spectrum, we have qualitatively evaluated the response of active absorbing layer structure and its photoelectric conversion properties of GaSb thermophotovoltaic device on the perturbation of external thermal radiation induced by the varying radiator temperature or emissivity. Our calculation has demonstrated that desirable thickness to achieve the maximum conversion efficiency should be decreased with the increment of radiator temperature and the performance degradation brought by any structure deviation from its optimal one would be stronger meanwhile. For the popular radiator temperature, no more than 1500 K in a real solar thermophotovoltaic system, and typical doping profile in GaSb cell, a reasonable absorbing layer structure parameter should be controlled within 100-300 nm for the emitter while 3000-5000 nm for the base.

Composite electrode for unitized regenerative proton exchange membrane fuel cell with improved cycle life

To improve the cycle life of unitized regenerative fuel cells (URFCs), an electrode with a composite structure has been developed. The cycle life and polarization curves for both fuel cell and electrolysis modes of URFC operation were investigated. The cycle life of URFCs was improved considerably and the performance was fairly constant during 25 cycles, which illustrates that the composite electrode is effective in sustaining the cyclic performance of URFCs. It shows the URFCs with such an electrode structure are promising for practical applications. (C) 2004 The Electrochemical Society.

Blends based on sulfonated poly[bis(benzimidazobenzisoquinolinones)] and poly(vinylidene fluoride) for polymer electrolyte membrane fuel cell

A new blend system consisting of an amorphous sulfonated poly[bis(benzimidazobenzisoquinolinones)] (SPBIBI) and the semi-crystalline poly(vinylidene fluoride) (PVDF) was prepared for proton exchange membranes. The miscibility behavior of a series of blends of SPBIBI with PVDF at various weight ratios was studied by WXRD, DSC and FTIR. The properties of the blend membranes were investigated, and it was found that the introduction of PVDF in the SPBIBI matrix altered the morphological structure of the blend membranes, which led to the formation of improved connectivity channels. For instance, the conductivity of the blend membrane containing 10 wt% PVDF displayed the highest proton conductivity (i.e., 0.086 S cm(-1)) at room temperature, a value almost twofold that of the pristine SPBIBI membranes (i.e., 0.054S cm(-1)) under identical conditions.

A new flow field and its two-dimension model for polymer electrolyte membrane fuel cells (PEMFCs)

A new flow field was designed to search flow fields fitting polymer electrolyte membrane fuel cells (PEMFCs) better due its extensible. There are many independent inlets and outlets in the new flow field. The new flow field we named NINO can extend to be more general when pressures at the inlet and outlet vary and some usual flow fields will be obtained. A new mathematical model whose view angle is obverse is used to describe the flow field.