Shuyan Qi

Synaptic pattern formation during cellular recognition

Cell–cell recognition often requires the formation of a highly organized pattern of receptor proteins (a synapse) in the intercellular junction. Recent experiments [e.g., Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. (1998) Nature (London) 395, 82–86; Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221–227; and Davis, D. M., Chiu, I., Fassett, M., Cohen, G. B., Mandelboim, O. & Strominger, J. L. (1999) Proc. Natl. Acad. Sci. USA 96, 15062–15067] vividly demonstrate a complex evolution of cell shape and spatial receptor–ligand patterns (several microns in size) in the intercellular junction during immunological synapse formation. The current view is that this dynamic rearrangement of proteins into organized supramolecular activation clusters is driven primarily by active cytoskeletal processes [e.g., Dustin, M. L. & Cooper, J. A. (2000) Nat. Immunol. 1, 23–29; and Wulfing, C. & Davis, M. M. (1998) Science 282, 2266–2269]. Here, aided by a quantitative analysis of the relevant physico-chemical processes, we demonstrate that the essential characteristics of synaptic patterns observed in living cells can result from spontaneous self-assembly processes. Active cellular interventions are superimposed on these self-organizing tendencies and may also serve to regulate the spontaneous processes. We find that the protein binding/dissociation characteristics, protein mobilities, and membrane constraints measured in the cellular environment are delicately balanced such that the length and time scales of spontaneously evolving patterns are in near-quantitative agreement with observations for synapse formation between T cells and supported membranes [Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221–227]. The model we present provides a common way of analyzing immunological synapse formation in disparate systems (e.g., T cell/antigen-presenting cell junctions with different MHC-peptides, natural killer cells, etc.).

CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse

How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering.

Transient instability upon temperature quench in weakly ordered block copolymers

We report a novel transient instability upon temperature quench in weakly ordered block copolymer microphases possessing a soft direction or directions, such as the lamellar and hexagonal cylinder (HEX) phases. We show that reequilibration of the order parameter is accompanied by transient long wavelength undulation of the layers or cylinders—with an initial wavelength that depends on the depth of the temperature quench—that eventually disappears as the structure reaches its equilibrium at the new temperature. Such undulation leads to a transient transverse broadening of the scattering peaks near the Bragg positions. We argue that this instability might be responsible for the experimentally observed unusual ordering dynamics of the HEX phase of a diblock copolymer after quenching from the disordered state.

Microphase segregation in molten randomly grafted copolymers

We study microphase ordering of molten randomly grafted copolymers (RGCs) by using a mean field theory and the replica method to calculate the quenched average. Our results illustrate that in the weak segregation limit (WSI), the optimal wave vector q* of the lamellar phase formed by molten RGCs, has a temperature dependence different from either linear random copolymers (LRCs) or diblock copolymers (DCPs): when close, but below the microphase separation transition (MST) temperature, q* increases sharply with decreasing temperature; then q* gradually acquires an asymptotic value determined by the length of the branch and the average distance between branch points on the backbone. Our results are compared with recent experiments, and the effects of chain architecture on the microphase separation characteristics of RGCs are delineated. Our results suggest a new method for controlling the microphase spacing by exploiting quenched disorder.

The phase diagram of molten randomly grafted copolymers

We study the microphase segregation of molten randomly grafted copolymers (RGCs) using a Landau field theory. Under one wave number approximation, we find three equilibrium ordered microphases: lamellar phase (LAM), hexagonal cylinder phase (HEX), and bcc sphere phase (BCC). The stability of these phases strongly depends on the architectural parameters describing the RGC chains (e.g., the backbone length, the branch length, and the number of branches). Our calculation reveals that RGCs with high average composition of backbone monomers or with low branching density tend to form LAM microstructures. For a small average composition of backbone monomers, HEX and BCC microphases appear in turn with increasing branching density. Independent of the architectural parameters and composition, the disorder to order transition for molten RGCs is always from the disordered phase to the LAM microphase. The physical reasons underlying this behavior and experimentally testable predictions are discussed.

Micelle formation of randomly grafted copolymers in slightly selective solvents

Amphiphilic surfactants, molecules with chemical moieties that interact differently with the solvating medium, are important for technological applications and ubiquitous in biology. Understanding how to control surfactant properties is, therefore, of wide-ranging importance. Using a combination of light scattering experiments and field theory, we demonstrate that the behavior of polymeric surfactants can be controlled sensitively by manipulating molecular architecture. We find that branched polymeric amphiphiles can be much better surfactants than traditional linear analogs. This is indicated by micelle formation in solvents that are very slightly selective for the backbone of the branched molecule. Our experimental and theoretical findings also suggest that, for a given chemistry and architectural class, surfactant properties of polymeric amphiphiles are very sensitive to subtle changes in architectural features. Specifically, we find that choosing a particular branching density optimizes the propensity...

Theoretical study of polymeric mixtures with different sequence statistics. I. Ising class: Linear random copolymers with different statistical sequences and ternary blends of linear random copolymers with homopolymers

We derive a Landau free energy functional for polymeric mixtures containing components with different sequence statistics. We then apply this general field theory to two mixtures that belong to the Ising universality class: mixtures of two different linear random copolymers, and ternary systems of linear random copolymers and two homopolymers. We discuss the instability conditions for the homogeneous state of these mixtures, and calculate the structure factors for different components in the homogeneous state. The structure factors show interesting features which can directly be compared with scattering experiments carried out with selectively deuterated samples. We also work out the eigenmodes representing the least stable concentration fluctuations for these mixtures. The nature of these concentration fluctuations provides information regarding the ordered phases and the kinetic pathways that lead to them. We find various demixing modes for different characteristics of the two mixtures (e.g., average co...

Theoretical study of polymeric mixtures with different sequence statistics. II. Brazovskii class: Linear random copolymers with diblock copolymers

We use a Landau theory to study the instability of the homogeneous state of a mixture of linear random copolymers and diblock copolymers. Interesting features of the calculated structure factors for different components of the mixture are found, which can be directly compared with scattering experiments with selectively deuterated samples. We also investigate the least stable concentration fluctuations and find four different types of segregation modes at the spinodal depending upon the characteristics of the mixture (e.g., average compositions, statistical correlation lengths and volume fractions). The different segregation modes are also indicative of the kinetic pathways leading to the formation of ordered microstructures. Experiments probing these pathways are suggested.