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From page 104... ... Basic physical limits to this mode of communication have been known for decades, but there still are new discoveries being made as the commu nity generalizes these ideas to contexts more relevant to real cells. In some systems, foundational work in biology has provided a nearly complete list of the relevant molecules, so there is a closed system within which to ask about the representa tion of information and the physical principles that govern life's choice of this representation. Read the entire page →
From page 105... ... This work in the biological physics community was contemporary with the first measurements of electrical current flow through nanoscale devices in the condensed matter physics community. For decades, this research program was in the reductionist spirit, finding the elementary building blocks that generate the electrical behaviors of cells. Read the entire page →
From page 106... ... If this is correct, then small patches of membrane will have small numbers of these channel molecules, and since single molecules behave randomly, the resulting current flow will have measurable randomness or noise, and it does. FIGURE 2.7 The macroscopic electrical dynamics of cells results from the underlying dynamics of specific protein molecules -- ion channels -- that are embedded in the cell membrane. Read the entire page →
From page 107... ... In a different direction, electrical signaling through action potentials, or through smaller amplitude graded changes in voltage, provide concrete examples where we can understand the energy costs of coding and computation in the nervous system. Our understanding of the inherently stochastic molecular dynamics of the channel molecules also means we can characterize the reliability or fidelity of information transmission and processing, and relate these measures of performance to the Read the entire page →
From page 108... ... Approaching the brain's output, one can once again see the correlation of single spikes and patterns of spikes with particular trajectories of muscle activity. The biological physics community has been keenly interested in the more ab stract properties of the code by which sensory signals and motor commands are represented by sequences of action potentials. Read the entire page →
From page 109... ... Alternatively, many tasks require organisms to make predictions, and perhaps it this predictive information which is almost always relevant. These ideas have deep connections to many problems in statistical physics and dynamical systems, and have even led to experiments that estimate the amount of information that small populations of neurons carry about the future of their sensory inputs. Read the entire page →
From page 110... ... Theories of collective behavior make predictions for the structure of measurable correlations, but one can also turn the argument around and ask for the simplest collective states that are consistent with the measured correlations. These ideas are deeply grounded in statistical physics, and have con nections to other examples of emergent behaviors of living systems, as discussed in Chapter 3. Read the entire page →
From page 111... ... The fly experiences virtual reality while electrical activity of neurons in the ellipsoid body is monitored through calcium-sensitive fluorescent proteins (Chapter 3) Read the entire page →
From page 112... ... Bacterial communication could be a byproduct of more basic pro cesses: As bacteria grow and move through a medium, they consume resources, and other bacteria navigate the resulting concentration gradients. But it had been known since 1970 that single celled organisms can communicate more directly, and in parallel with the biological physics community's interest in pattern formation, microbiologists were exploring the molecular basis of this communication and realizing that it is widespread among bacteria. Read the entire page →
From page 113... ... More modestly, cells make decisions to attach to surfaces and grow communally only when there are enough compatriots in the neighborhood. As with modern work from the biological physics community on flocks and swarms (Chapter 3) Read the entire page →
From page 114... ... Bassler, 2016, Vibrio cholerae biofilm growth program and architecture revealed by single-cell live imaging, Proceedings of the National Academy of Sciences U.S.A. 112:E5337, Creative Commons License CC BY-NC-ND 4.0. Read the entire page →
From page 115... ... In some ways this is similar to the ability of bacteria to swim toward sources of nutrients by sensing the concentration of the relevant molecules along the way (chemotaxis, Chapter 1) , but the physics in these two cases is very different. Read the entire page →
From page 116... ... Vocal Communication Our human preoccupation with vocal communication leads to special interest in other animals that use the same modality. Frog calls, bird songs, and the mys terious sounds of whales and dolphins all attract our attention, and the attention of the physics community. Read the entire page →
From page 117... ... As discussed in Chapters 4 and 7, these models have their roots in statistical physics models for networks of real neurons in the brain, and many people see statistical physics as a natural language Group within which to understand why such systems work so well. Among other features, Read the entire page →
From page 118... ... Perspective The biological physics community's exploration of communication spans from hydrodynamic trigger waves to language, from songbirds to information-based search, and more. From the biological point of view, these are vastly different sys tems, the subjects of quite separate literatures. Read the entire page →
From page 119... ... For a single cell, this behavioral scale is on the order of microns, something visible only through a microscope but still a thousand times larger than the nanometer scale of individual molecules. A major thrust of biological physics is to understand how to bridge these scales, from microscopic to macroscopic. Read the entire page →
From page 120... ... Rather in each case, the biological physics community has uncovered exciting new ques tions, focusing attention on how the emergent phenomena of life are different from their counterparts in the inanimate world. A sampling of these efforts is given in Table 3.1. Read the entire page →
From page 121... ... Collective 152 Understanding the beautiful, New universality classes; Active matter; behavior coordinated movements direct inference of coordination of birds in a flock, insects statistical physics models of autonomous in a swarm; emergence of from data; non-classical vehicles. "construction projects" in modes of ordering. Read the entire page →
From page 122... ... It would take decades until the first protein structures were revealed through the analysis of X-ray diffraction patterns, in the late 1950s and 1960s. These struc tures were not so precise as to reveal the positions of individual atoms, but showed clearly that the polymer of amino acids folded into local or "secondary" structural elements, helices and sheets, as had been predicted theoretically; these elements then pack into the overall globular structure of the protein. Read the entire page →
From page 123... ... (C) Modern high resolution structure of one hemoglobin subunit, focusing on the heme and nearby amino acids. Read the entire page →
From page 124... ... Some measure of the impact of these develop ments is in the stream of Nobel Prizes recognizing many of the breakthroughs: the first structures of proteins and other complex biological molecules (1962, 1964) ; the use of electron microscopy to solve structures with repeating units, as with the many proteins in certain viruses (1982) Read the entire page →
From page 125... ... do not. Protein structures pack the hydrophobic amino acids into the core, leaving a shell of hydrophilic amino acids to interact with the surrounding water. Read the entire page →
From page 126... ... determinants of protein folds suggest that these proteins generally fold in modules, in other words, This discussion Secondary structure, the has emphasized helices and sheets that arethe foundconceptual every native protein structure, is stabilized primarily by hydrogen in nearly problems of protein folding, folding can take place largely independently in different segments or domains of the protein6,14. In such cases, interactions involving key how and why well-defined structures emerge NATURE \| VOL 426 \| 18/25 DECEMBER 2003 \| www.nature.com/nature from interactions among amino acids. Read the entire page →
From page 127... ... This is the "protein design problem." These questions are discussed in Chapter 6, which describes the connections among biological physics and molecular and structural biology. Applications of these ideas in the search for proteins with engineered functions are discussed in Chapter 7. Read the entire page →
From page 128... ... Perspective Proteins represent a different organizational state of matter than is found in the non-living world, selected by evolution for particular functions but also for the more general task of folding efficiently into compact structures. The great expan sion of experimental methods for determining protein structures, now largely ex ported from biological physics into the structural biology community, encourages us to think more globally about the mapping between sequence and structure. Read the entire page →
From page 129... ... Thanks to generations of experiments, one can point to the physical location of these many functional pieces along the genome. But despite this detailed information, it still is not known how these regulatory elements, which are often separated from their target genes by thousands to millions of base pairs along the DNA, manage to find and activate their specific target genes. Read the entire page →
From page 130... ... ChromEMT reveals the in situ chromatin ultrastructure, 3D packing, of DNA. that selectivity enhancesFIGURE 3.4 Theand the contrast double helix of DNA is packed into the cell nucleus through a series of higher order organization of DNA. Read the entire page →
From page 131... ... This scale is roughly 100× larger than the nucleosome, leaving a substantial gap in our understanding. Importantly, the missing scales overlap the scale of DNA regulatory elements in higher organisms, so what is missing is very relevant for how information flows through genetic networks (Chapter 2) Read the entire page →
From page 132... ... . Ideas from statistical physics have been used to identify the origin of these dynamics and to demonstrate that the robust scaling laws observed for chromosomal motion in vivo can arise from physical principles rather than system-specific biological mechanisms. Read the entire page →
From page 133... ... in a mammalian cell nucleus, shown in a two-dimensional projection. Read the entire page →
From page 134... ... It had long been known that purified versions of biological materials had interesting phases and transitions, but except in special cases -- such as the behavior of proteins in the lens of the eye -- it was never clear that this physics was relevant to the business of life. Over the course of a decade, this has changed dramatically, with novel phases, phase transitions, and phase separation becoming central to discussions of myriad processes in living cells. Read the entire page →
From page 135... ... Near criticality, there are fluctuat ing domains on long length scales, and the spatial and temporal statistics of these fluctuations are predicted theoretically, by general statistical physics principles, with no free parameters; these predictions have been confirmed in detailed experiments on these membrane systems. The surprise is that real biological membranes have lipid compositions close to the critical point. Read the entire page →
From page 136... ... The observation of liquid-liquid phase separation in the two dimensions of a membrane prepares us for the possibility that something similar happens in three dimensions with proteins and nucleic acids in the cytoplasm. Phase Separation in the Cytoplasm Understanding the principles that drive the organization of biological molecules into function-specialized machines known as organelles has been largely undertaken by biologists, not physicists. Read the entire page →
From page 137... ... However, although the components of the disordered non-membrane bounded organelles were identified, the disordered nature of their structure and difficulty in achieving in vitro reconstitution made it difficult for biologists to decipher the physical principles driving their highly ordered formation. It came as a surprise that structurally disordered, non-membrane-bounded or ganelles form by the process of liquid-liquid phase separation. Read the entire page →
From page 138... ... a quantitative description of the relationship between valency, affinity, concentra tion, and phase separation, which was similar to transitions from small complexes to large, dynamic supramolecular polymers that had been described in non-living systems. Subsequent demonstrations that phase separation actually affects protein activity led to the notion that phase transitions may be used to spatially organize and biochemically regulate information throughout biology. Read the entire page →
From page 139... ... Instead, cells are responsive to the mechanical properties of their surroundings, which can affect their motility, shape and even decisions about which genes to express. The biological physics community has been interested in all these problems, and has had strong interactions with the larger community of cell biologists, as described more fully in Chapter 6. Read the entire page →

From page 104...

... Basic physical limits to this mode of communication have been known for decades, but there still are new discoveries being made as the commu nity generalizes these ideas to contexts more relevant to real cells. In some systems, foundational work in biology has provided a nearly complete list of the relevant molecules, so there is a closed system within which to ask about the representa tion of information and the physical principles that govern life's choice of this representation.