Richard Skalak - US grants

mathematical model; growth /development;

This proposal will provide partial funding for the "1st World Congress of Biomechanics". This new international conference will provide a useful and coordinated mechanism for the dissemination of knowledge in this new and growing field of engineering. Topics to be covered will include both current research and projections for future needs and trends in biomechanics research. It is the intent of the organizers of this meeting to consolidate the various small national and international meetings into a single large one, so that an interdisciplinary synergism can enrich the field of biomechanics.

Experimental and theoretical investigations of possible mechanisms of backflow of information in neurons are proposed. Such retrograde flow of information is a crucial aspect of learning and plasticity of neural networks involving backpropagation. The experimental preparations to be used are hippocampal slices of the rat brain. Evidence of retrograde pathways of informational flow other than membrane electrical potentials will be sought. One stimulus will be mechanical compression of efferent axons or axon hillocks. Changes in synaptic response at the dendritic and axonal levels will be monitored as evidence of backpropagation. The time scale of interest will be milliseconds as opposed to slower processes of axonal cytoplasmic flow in either direction. If functional plasticity is demonstrated, electron- microscopic examination of synapses will be made to seek cytoskeletal or vesicle alterations that correlate with the functional changes. Theoretical models will consist of cytoskeletal components of actin-myosin gel, microtubular structure and a viscoelastic matrix representing cytoplasm. An active tension will be assumed in the actin-myosin gel. Possible modes of wave propagation in the composite structure will be investigated. The significance of the proposed research will be very important of correlation of biological counterparts to theoretical models of neural networks.

The First World Congress of Biomechanics is planned in order to establish an international forum for the exchange of current research progress in all areas of biomechanics. The Congress will be held at the University of California, San Diego (UCSD) in La Jolla, California, August 30 - September 4, 1990. The Congress has been organized by an International Steering Committee, Professor Y. C. Fung, Chairman. This International congress will bring together various national groups and researchers, interested in different aspects of biomechanics for the comprehensive evaluation of current achievements and the identification of promising directions for future research. The topics to be covered include: Molecular and cellular mechanics, cardiovascular mechanics, respiratory mechanics, dental mechanics, orthopaedics and musculoskeletal mechanics, muscle mechanics and sports medicine, tissue engineering related to trauma, growth and replacements, animal mechanics and locomotion. The emphasis of the Congress will be on biomedical research in which mechanics plays a central role. The holding of this Congress promises to exchange scientific information, stimulate research interests, generate innovative ideas, and open new horizons in biomechanics, and the results will ultimately benefit the health and welfare of mankind.

An Institute of Mechanics and Materials (IMM) is being established at the University of California at San Diego to integrate research and industrial applications in mechanics and materials. The Institute will foster interdisciplinary communication and liaison between academia, industry and governmental organizations. The principal activities will include short courses on frontier, interdisciplinary areas; workshops on specific industrial problems and innovative materials; and short and intermediate length visits of graduate students, post-doctoral fellows, faculty members, and scientists and engineers form government laboratories and industrial organizations. The Institute will not conduct extensive research projects, per se, but will aim to serve as an intellectual forum to catalyze the formation of research groups when new areas or methods of approach are identified. This will include novel techniques for materials development, synthesis and processing; characterization and identification of properties-microstructure relations; physically-based micromechanical and computational modeling; and constitutive relations for nonlinear response and failure analysis; as well as design and performance analysis of complete structural entities. Timely topics will be discussed in think-tank-style workshops which will also be used for periodic assessments of long-term goals in mechanics and materials science and engineering. An external Board of Governors of prominent senior scientists and engineers will direct the Institute activities through action subcommittees and regularly assess the Institute's progress. The educational efforts of the Institute will include all levels of engineers and scientists in academia, industry and government (both national and international); and a strong outreach program to high school students and their teachers on a nationwide basis wherever there is interest, with a deliberate effort to reach minorities and under-represented segments of the population, as well as the gifted.

This proposal seeks to explain movements of the body of the leech, Hirudo medicinalis, in terms of the forces generated by its muscles and by the arrangement of these muscles in the body wall. In addition to moving the animal, these muscles also produce a stiff tube which constitutes a "hydrostatic skeleton". There is no general theory for such a skeleton that would allow us to predict the shape of the animal's body from the activity pattern of its motor neurons. Therefore, the goal of this proposal is to use a combination of experimental measurements and numerical simulations to derive a quantitative description of hydrostatic skeletons in general and of the leech in particular. This study will proceed in three steps: 1. Describing leech movements in biomechanical terms. Segmental volumes, muscular tensions, geometric relationships of the muscles, internal pressures, and fluid flows will be determined. 2. Developing an analytical model of hydrodynamic skeletons. The current best model will be expanded to produce more realistic body forms, using the physical measurements obtained above. 3. Refining the model by comparing its performance to behaviors. Measurements during the production of simpler behaviors (bending and shortening) will be used to determine parameters which will tested by the model's ability to produce the more global behaviors (swimming and shortening). Such a model should be applicable to other hydroskeletons as well.***

The objectives of the conference are to develop an integrated view of the structure and surface properties of implants from the standpoint of the cellular-level responses of biological tissues to non-biologic materials and to survey current clinical rehabilitation needs in regard to performance of implanted biomaterials. The conference aims to bring together scientists from three major areas: materials science, cell biology, and clinical rehabilitation medicine. The conference will be jointly sponsored by the Institute for Mechanics and Materials (Professor Richard Skalak, Director) and the Institute for Biomedical Engineering (Dr. Shu Chien, Director). Both of these Institutes are located at the University of California at San Diego in La Jolla, California, which will also be the venue of the conference. The Institute for Mechanics and Materials represents a national constituency in materials scientists who are not generally in touch with biological research or rehabilitation needs. Members of the Institute for Biomedical Engineering include expertise in cell biology but are not, in general, materials scientists. The aim of the conference is to bring these diverse groups together and to seek practicing clinicians' advice of current rehabilitation medicine needs in regard to biomaterials. The scientific focus of the conference will be on cellular responses to implanted materials. This is the bridge-head area connecting the three main disciplines involved. It is anticipated that new joint research projects in biomaterials research for clinical rehabilitation purposes will result from this conference.

9402824 Skalak This proposal from University of California at San Diego requests partial support to conduct a conference entitled Biomaterials: Cellular Response to Implanted Materials. The symposium focuses on integration of the structure and surface properties of implants form the standpoint of the cellular level responses of biological tissues to non- biological materials and to survey current clinical rehabilitation needs in regards to the performance of implanted biomaterials. The aim of the conference is to bring together materials scientists, cell biologists and practicing clinicians in rehabilitation medicine. %%% Presenter participants in the symposium are world leaders in biomaterials, cell biology, and clinical rehabilitation medicine. Funding requested from the NSF would provide partial support for invited participants. The results of the conference will be recorded in a Proceedings, which will be sent to all conference participants and to related organizations and agencies, thereby making symposium results available to a large audience. ***

9415483 Skalak This award is to conduct the annual NSF Design and Manufacturing Grantees Conference. The conference will involve researchers from the Division of Design, Manufacture, and Industrial Innovation and the Division of Engineering Education and Centers, both located within the Directorate for Engineering, and the Division of Information, Robots and Intelligent Systems, located within the Directorate for Computer and Information Science and Engineering. The conference ensures that the individual researchers are informed about the ongoing activities of their colleagues. An elimination of duplication of their efforts may be achieved and a degree of cooperation may result from this activity. An overall improvement of efficiency of the research activity could be expected. In addition, the conference program organization allows for ample time to discuss manufacturing research in detail with the collective research community at the meeting, with feedback to and input from the National Science Foundation. Finally personal contacts between the grantees and program directors in the Divisions should contribute to clarifying many current issues in their work. The aims of the conference are to enhance communication between researchers, encourage joint research, promote synergism, and develop networks for technical interchange. Attendees to the conference gain an early access to the information disseminated.

9512778 Schmid-Schoenbein Skeletal muscle represents the largest organ in the body. Normal contraction of muscle fibers depends on an intact blood flow in this organ, especially in the smallest blood vessels known as the microcirculation. The blood flow in the skeletal muscle microcirculation can be adjusted according to the activity of the muscle fibers. Understanding of blood flow in this organ is an essential element in understanding muscle performance and its failure. The overall objective of the PI's research project is to develop an analysis of blood flow in skeletal muscle from a basic point of view at the cellular and molecular level using rigorous physical language. The PI's previous NSF project has served to obtain basic elements of the analysis, including the actual network microanatomy of the vast number of blood vessels in the microcirculation, the biophysical properties of the blood vessels (arteries, capillaries and veins) and the blood fluid, the display of nerves, lymphatics, and other cells in the muscle. This information was integrated into an analysis of blood flow in resting non-contracting skeletal muscle which is based on basic biomechanical principles and implemented in form of a numerical computation on a digital computer by means of highly efficient algorithms. The predictions of the analysis were compared with all suitable experimental results in the skeletal muscle literature. In addition, the PI has carried out additional experiments on blood flow in skeletal muscle to test the analysis in quantitative details. The analysis provides the first time a comprehensive picture of skeletal muscle blood flow with physical precision. While this approach serves to explain a large number of experimental observations in the past, it has also lead to several discoveries including the following: 1) The basis for the specialized relationship between pressure, which drives the blood in skeletal muscle and blood flow, was identified and its physical origin was identified. 2) The identification of the mechanism that leads to cessation of muscle perfusion during pressure pulsations. 3) The identification of a previously undescribed mechanism for lymph flow in skeletal muscle. Recently, evidence has been obtained for a second valve system in the lymphatics of skeletal muscle, in addition to the well-known intralymphatic valve system. This observation provides the first time a comprehensive understanding of the mechanism by which lymphatics transport fluid and cells. 4) The identification of a new membrane function of the cells lining the blood vessels, i.e. the endothelial cells. 5) Analysis that served as the basis in leading to the discovery of a mechanism by which the small arteries in the microcirculation grow (research by the PI's former student Dr. T.C. Skalak at the University of Virginia, Charlottesville). 6) The discovery of a significant influence that circulating white blood cells have on the perfusion of skeletal muscle, especially when these white blood cells are activated. The PI has also identified a mechanism by which endothelial cells project small cytoplasmic extensions into the lumen of the microvessels in the activated state. These observations are important in regards to muscle fatigue. The proposed research serves as a direct expansion of the current analysis. The future analysis is directed at the following: 1) Expansion of the current analysis to the case of contracting muscle. During contraction, the skeletal muscle fibers compress the blood vessels of the microcirculation and therefore strongly influence the blood flow to the organ. 2) Identification of the biomechanical mechanism by which relatively few circulating white blood cells exert a significant influence on the perfusion of muscle microcirculation. 3) To study the influence of cytoplasm extensions on endothelial cells lining blood vessels on perfusion of the muscle microcirculation. The PI will continue to carry out the experiments on skeletal muscle in rats, so that all prev ious information serves as a basis for the future work without uncertainties regarding species differences. ***