Nonequilibrium dynamics is a thriving sub-field within physics that seeks to identify the principles underlying complex spatiotemporal patterns that arise in far from equilibrium systems. Living biological organisms are one important subclass of systems far from equilibrium, yet, due to their complexity and variety, they have remained relatively understudied by theorists and experimentalists alike. As such, significant questions exists both about the extent to which methods of nonequilibrium dynamics can be used to identify laws governing pattern formation and regularities in biological organisms. Funds from this grant support Jeff Gore, Nikta Fakhri, and Jörn Dunkel of MIT in a series of projects that will begin to examine whether and how nonequilibrium dynamics might be used as an organizing framework for understanding how ordered biological phenomena arise and evolve across a variety of scales. Topics to be explored by the team include the role of topology and topological defects in triggering order-enhancing processes in starfish cells; the assembly of ordered structures of colloidal molecules by motile bacteria; and how spatial distribution affects the evolution and ecology of microbe populations. In addition to knowledge gained, the project will involve the development and deployment of new imaging and theoretical analysis tools, expanding the available methods for the thermodynamic study of biological systems.

Natural cells routinely use shape as a vector for acquiring and disseminating information about their environment.  Detecting the shape of a cell they have encountered can impart important information about their neighbor, and thus inform what sort of response would be most adaptive.  The underlying mechanisms that allow organisms to process this topological information, however, are not well understood.  This grant funds a multi-disciplinary a team led by Ronit Freeman at the University of North Carolina at Chapel Hill to better understand these mechanisms by attempting to create an artificial cell-like entity that mimics natural cells’ ability to detect shape.  Grant funds will support three interrelated research efforts. We know that cells use proteins to detect the shape of fellow cells, but the proteins that perform this function can be 10 to 100 times smaller than the cells they are measuring.  How these natural systems bridge that length gap is poorly understood.  Using advanced atomic scale microscopy, Freeman’s team will observe the behavior and structure of these shape-detecting proteins and attempt to reverse engineer synthetic versions that could perform similar functions in a synthetic cell. A second effort will focus on signal transduction, the process of converting shape data collected at the cell membrane into physical and biochemical signals that can be passed to a cell’s interior.  The research team will attempt to create synthetic pathways that mimic signal transduction mechanisms thought to operate in natural cells, allowing them to use detected topological information to effect changes in behavior of the synthetic cell itself.  Third, the team will use advanced techniques to model how topological information can spread through communities of cells, affecting the behavior or characteristics of entire cell collectives.  Such modeling has, to date, mainly confined itself to the chemical aspects of cellular communication. Freeman and her team will expand these efforts, incorporating physical variables such as the flow of mass and momentum, membrane elasticity, flow across interfaces, and cell deformation into their model.

A Cornell University team led by Paul McEuen has developed a fully artificial platform with some remarkable capabilities.  The platform's basic building blocks—magnetic digital polymers—are small panels (a few microns) with magnetic data lithographically patterned on their faces and sides. These data specify via magnetic forces how the panels interact with one another.  This ingeniously allows the panels to mimic the chemistry of biological molecules.  In biological molecules, the atoms that make up a molecule determine which other molecules it can chemically bond with and how strong such a bond, once formed, is.  By altering the data pattered on the faces of the digital polymers, McEuen and his team can replicate these features, with some polymers bonding selectively with others, just like biological molecules do.  What’s more, because the physics of magnetism is well-understood, the behavior of McEuen’s magnetic polymers should be relatively simply, at least in theory, to model and predict. This grant funds an effort by McEuen and his research team to attempt to use magnetic digital polymers to mimic two important features of biological life: reproduction and metabolism. To demonstrate "reproduction" McEuen and his team will begin by developing what they call Magnetic DNA, a digital magnetic polymer capable of replicating itself. Reproduction will be demonstrated by programming in appropriate magnetic interactions to create information strands (polymer patterns) that self-replicate under cyclic application of “agitation” via an external magnetic field, acoustic waves, and/or thermal excitation. To demonstrate "metabolism," the team will use a variety of strategies to create a magnetic polymer version of an enzyme, an entity that can modify the replicating unit. This will involve using magnetic and mechanical forces to cut linear polymer chains at specified locations, in analogy to how the CRISPER-Cas9 protein cuts DNA.

Speculation about the existence of other life in the universe has become invigorated in recent decades by an explosion in the discovery of extrasolar planets.  The numbers tell the story. There were about 50 known exoplanets in year 2000, about 500 known by 2010, and we're approaching 5,000 today.  Powerful telescopes can reveal information about the chemical composition of the atmospheres of these far away planets.  Can they also tell us if there is life there?  They could if the atmospheres of planets with biospheres differed systematically from the atmospheres of lifeless planets, Knowing that, however, would require knowing what the atmosphere of a lifeless planet looks like, and how life might change it. This grant funds an effort led by Anan Shahar at the Carnegie Institution for Science to determine the abiotic atmospheric baseline of the most common planets in our galaxy, sub-Neptune and rocky planets. With the abiotic baseline known, scientists can then consider how Earth-like life might change a planet's atmosphere and in this way tackle the question of whether or not it's possible to determine signatures of life by studying exoplanet atmospheres The research team will pursue an interdisciplinary, holistic approach that combines solid-planet expertise with atmospheric expertise in order to understand the baseline abiotic atmosphere of a planet and how it evolves over the planetary lifecycle.  What’s called a planet’s primary atmosphere is formed early in a planet’s  formation, as the planet coalesces from matter orbiting a local star.  This atmosphere then evolves into a secondary atmosphere, one shaped both by geologic processes on the planet itself (volcanism, magma oceans, outgassing, the weathering of the planet’s surface) and by external forces like comet impacts.  The research team will attempt to model and the analyze the effects of these forces, shedding light on how the atmospheres on lifeless planets are likely to evolve across the planetary lifecycle.  

The interior of a cell is a chaotic, turbulent place dominated by random, thermally driven collisions.  Inside this tempest, the internal structures of a cell must do their delicate work.  The creation of a single strand of mRNA, essential for creating the proteins that make cells run, requires the meticulous assembly of long sequences of adenine, cytosine, guanine, and uracil.  Yet despite the ever present internal squall and the exacting nature of the work, these cellular processes have surprisingly low error rates.  The chance of a transcription error inside e. coli bacteria, for example, has been observed to be about 1 in 10,000.      Explaining how such high accuracy is achieved under such adverse conditions is an enduring challenge for biology.  This grant funds a series of experiments designed by Rockefeller University’s Gregory Alushin, Amy Shyer, and Shixin Liu that explore one promising explanation: mechanical force. Alushin, Shyer, and Liu will use grant funds to field two research projects that use emerging technologies, such as high-resolution imaging and tools that apply and measure nanoscale forces, to explore the role played by mechanical force in two areas of biology. In the first, Alushin, Shyer, and Liu will work at the nanoscale to test the hypothesis that force influences the fidelity of the molecular machine that executes the primary step in gene expression, the copying of genetic information from DNA to RNA (transcription). This multiprotein machine is called RNA polymerase (RNAP) and the project team hypothesizes that force can cause RNAP to adopt structures that favor error correction during transcription. To test this, the team will exert forces on RNAP and measure the resulting error rates and structures. In the second project, the team will examine the role of force in morphogenesis, the development of heterogeneity in an initially uniform collection of cells (e.g., tissue) that underlies organ development. The team will use force manipulation and imaging to directly probe how force propagates across tissue-scale lengths while also mapping how force drives the molecular-scale rearrangements that launch gene expression. Here the principal investigators hypothesize that force propagates at a speed that exceeds what’s possible in models of chemical-signal propagation.