This award supports an international collaboration for research and education among Syracuse University in the USA, Bristol University in the United Kingdom, and the University of Stellenbosch in South Africa. This collaboration is for theoretical studies that will dramatically improve our understanding of the structure and mechanical properties of networks of cytoskeletal filaments and associated motor proteins, under both in vitro and in vivo conditions. An important outcome will be the identification of the relative importance of physical and biochemical mechanisms in controlling many cell functions, such as motility, force generation and division. The success of the proposed research relies crucially on the complementary expertise of the collaborating research teams in hydrodynamics and nonequilibrium physics (USA), in semiflexible polymer physics (UK) and on theories of polymer gels (South Africa). The first part of the research builds on work by the US and UK groups on purified (in vitro) cell extracts of cytoskeletal filaments and motor proteins (active liquids). By working closely with experimentalists in the US, UK and Germany, the researchers will focus on understanding how filament flexibility and microscopic properties of the motile elements (e.g., motor stiffness, dynamical properties and processivity) affect the macroscopic behavior of the active fluid. The second and major part of the proposal considers the new area of active solids: the cell cytoskeleton (in vivo) and in vitro gels of cytoskeletal filaments linked by both active (motor proteins) and passive crosslinkers. The proposed research will lead to an understanding of the fascinating linear viscoelastic behavior of active gels. Regular student exchange visits planned during this award period will provide mechanisms for close collaboration among the three groups and exceptional educational opportunities and international research experience.
The achievement of the scientific goals will be closely linked with a number of more general benefits. First, the research will provide significant scientific progress in areas relevant to physics, biology and biological and biomimetic materials. A better understanding of the processes controlling the complex mechanical properties of the cytoskeleton, the internal framework of a cell, can lead to important advances for the design of a new generation of smart materials at the nanoscale. The collaboration will also open the door, through visits to the African Institute for Mathematical Sciences (AIMS) located near Cape Town, to the establishment of contacts with gifted students in the mathematical sciences from throughout the African continent. Finally, student and postdoctoral researcher exchange among the collaborating groups will expose all team members, including undergraduate students, to research in an international setting. The relationships developed during these exchanges will serve as the foundation for continued collaborations, while promoting long-term International networking.
This award is jointly funded by the Division of Materials Research in the Mathematical and Physical Sciences Directorate and the Office of International Science and Engineering.
This Materials World Network award has supported an International collaboration for joint research and education between participants in the US, the UK and South Africa. The scientific outcomes of the project, described below, relied crucially on the complementary expertise of the US PI (Cristina Marchetti, Syracuse University, in hydrodynamics and nonequilibrium physics, the UK PI (Tannie Liverpool, Bristol University) in semiflexible polymer physics and the South African PI (Kristian Müller-Nedebock, University of Stellenbosch, South Africa) on theories of polymer gels. Intellectual Merit and Scientific Outcomes The cytoskeleton is a network of filamentary biopolymers (mainly actin and microtubules) that serves as muscle and skeleton of living cells. It provides the cells with mechanical support and mediates the transmission of forces within the cell and between the cell and its surrounding, mediating cell crawling, muscle contraction, and changes in cell shape in the developing embryo. It also supports transport inside the cell and the sorting of chromosomes during cell division. What distinguishes the cytoskeleton from more familiar and well-studied polymer networks is the presence of motor proteins able to undergo mechano-chemical reactions and convert stored chemical energy into mechanical work. Individual motor proteins ``walk" along individual biopolymers transporting cargos within the cell. Clusters of motor proteins function as active crosslinkers, capable of continuously remodeling the polymer network, driving and maintaining the system out of equilibrium. This collaborative project has focused on theoretical studies of the structure and mechanical properties of the cytoskeleton and its constituents (biopolymers and motor proteins), both in vitro and in vivo. This direction of research was inspired by developments in experimental techniques that have allowed the characterization of the physical properties of the cytoskeleton and its components at the cellular and sub-cellular scale. Specific scientific outcomes achieved during the lifetime of the award include: The characterization of the nonequilibrium patterns formed by suspensions of biopolymers and associated motor protein and the understanding of the rheology of these active fluids. This work is also directly relevant to bacterial suspensions that can be described as collections of ``swimmers" in a solvent. The PI and collaborators demonstrated theoretically that the viscosity of the suspension depends on the concentration and speed of bacteria, as well as on the type of swimming mechanism. Bacteria such as E. coli propelled from the rear decrease the viscosity as compared to that of the same liquid with nonmotile bacteria, while the alga Chalmydomonas propelled at the front increases the viscosity of the suspension. These finding have been confirmed by experiments. The formulation of a generic framework for the description of crosslinked polymer networks with internal stresses generated by active mechano-chemical reactions, such as the cell cytoskeleton. The work has yielded a phase diagram summarizing the three dynamical states through which the gel can be tuned by changing degree of motor protein activity: an unstrained state of uniform density, a state that supports spontaneous oscillations, and a spontaneously contracted state. These results are significant because they provide a possible mechanism for the spontaneous contraction and oscillation observed ubiquitously in living cells. The development of a simple, yet powerful continuum formulation for the description of cell-substrate interactions that accounts for several of the observed substrate-stiffness dependence of cell properties. Many cell functions, such as spreading, growth, differentiation and migration, are affected by the mechanical and geometric properties of the extracellular matrix or substrate on which the cell sits. The work supported by the project has demonstrated that the spatial variation of the traction stresses exerted by cells on substrates are controlled by a length scale and has provided an analytic expression for this length in terms of both cell and substrate properties. Broader Impacts The research carried out in this interdisciplinary project has impacted areas of biology, physics and biomaterials research. It has also provided: broad training and experience in international research for graduate students and postdocs at the interface of physics and biology; the strengthening of existing international collaborations with the UK and the establishment of new ones with South Africa. A unique outcome of this project has been the establishment of a strong connection between Syracuse and AIMS, the African Institute for Mathematical Studies, in Cape Town. AIMS is a center for the postgraduate education of African students. It offers one-year diploma courses to selected students from all-over Africa. As of today, six African students (four men and two women, from various countries, such as Rwanda, the Republic of Congo, Camerun, Madagascar and Ethiopia) have come to Syracuse for graduate studies through this partnership. The first three who came in 2008 are close to finishing their doctoral studies. The African students have integrated well with their fellow graduate students and have been generally successful as teaching assistants. They have greatly increased the diversity of our student body and serve as role models to our undergraduate population.
