Condensed-Matter and Materials Physics The Science of the World Around Us (2007) / Chapter Skim
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4 What Is the Physics of Life?
4 What Is the Physics of Life?
Pages 70-90
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From page 70... ...
Already, burgeoning understanding is leading to an unprecedented degree of collaboration between CMMP scientists and biologists, on problems ranging from why proteins misfold and form unwanted structures in diseased tissues, as in Alzheimer's disease, to how the brain works. CMMP will continue to catalyze advances in biology and medicine by providing new methods for quantitative measurement, from rapid genomes equencing techniques to novel medical diagnostics.
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From page 71... ...
An Introductory Example: High Fidelity with Single Molecules One of the central problems faced by any organism is to transmit information reliably at the molecular level. This problem was phrased beautifully by Schrödinger in "What Is Life?
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From page 72... ...
, but the idea is the same. The messenger RNA also has a sequence of bases, and these are read once more, now in groups of three, to determine the sequence of amino acids in proteins, yet another kind of polymer inside the living cell.
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From page 73... ...
Hopfield's theory of kinetic proofreading, along with the related ideas of Jacques Ninio, made many successful experimental predictions, and the essential idea of kinetic proofreading has proven correct. Subsequent theorists have suggested yet more examples in which biology achieves paradoxically precise function at a molecular level and thus in which some version of proofreading may be at work, from the specificity of cellular signal transduction to the untangling of the strands of the double helix.
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From page 74... ...
Almost certainly this reflects the elementary steps of proofreading. Techniques based on fluorescence energy transfer between nearby molecules are giving glimpses of the proofreading steps in transla tion from messenger RNA to protein, again at the level of single molecules.
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From page 75... ...
Interactions between molecules involve energies of just a few times the thermal energy, and biological motors, including the molecular components of muscles, move on the same scale as Brownian motion. Biological signals often are carried by just a few molecules, and these molecules inevitably arrive randomly at their targets.
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From page 76... ...
When one or more of the motors spin in the clockwise direction, the bundle is disrupted and the cell tumbles and makes little forward progress. The switching between forward and tumbling motion causes the cell to undergo a (potentially biased)
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From page 77... ...
-- a molecule that is widely used in biochemical reactions that need energy in order to go forward. But all living cells synthesize ATP using the chemical potential difference for protons across a membrane, and the enzyme that carries out this synthesis rotates as it performs its function.
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From page 78... ...
Genetic techniques have identified a cascade of molecular events that lead from receptors at the cell surface to the rotational bias of the flagellar motor. Combin ing methods from molecular biology and physics, one can engineer bacteria that produce fluorescent analogs of these molecules and then use a variety of optical methods to observe the individual steps of this amplifying cascade.
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From page 79... ...
In fact, cells have access to a "dial" that can be set accurately to many distinct expression levels. Quantitative measurements of the way in which noise levels vary as a function of the mean expression level have driven theoretical efforts to dissect the contribu tion of different noise sources.
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From page 80... ...
and intrinsic components. As explained in the text, the intrinsic noise can be quite low, so that expression levels can be set by the cell with roughly 10 percent accuracy.
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From page 81... ...
Signals that determine 4-4 a,b,c,d,e the location of these structures are detectable as spatial patterns in the expression levels of different genes, two of which are made visible here in orange and green (top right)
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From page 82... ...
The exploration of photon counting in vision reaches from the analysis of human behavior down to the level of single molecules, with many physics problems at every level. For example, it is not just that one can count single photons; the reliability of counting seems to be set by "dark noise" in the photodetector cells of the retina, and this noise in turn is dominated by thermal activation of the molecule (rhodopsin)
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From page 83... ...
Recent work along these lines includes the demonstration that, under certain conditions, the fly's visual system can estimate motion with a precision limited by noise in the receptor cells of the compound eye, and that this noise in turn is dominated by photon shot noise. Making optimal estimates in the presence of noise requires some prior hypotheses about what to expect, and it has been suggested that illusions -- in particular, illusory motion percepts -- can be understood, perhaps even quantitatively, as violations of these hypotheses.
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From page 84... ...
But this simple structure can be frustrated by the fact that the dif ferent amino acids are linked, covalently, along the length of the polymer. Indeed, a result from statistical mechanics states that a random polymer in which different monomers have competing interactions will be so frustrated that it forms a glass, with many distinct structures having nearly equal energy.
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From page 85... ...
These ideas of a smooth "energy landscape" and minimal frustration grow directly out of investigations on problems in CMMP, and over the past decade this theoretical picture of protein folding has scored important successes in connecting directly to a wide variety of experiments. Ideas from statistical physics also have been important in defining the "inverse folding" problem: given a particular compact protein structure, is there an amino acid sequence that folds to this structure as its ground state?
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From page 86... ...
These dynamics depend on how many channel molecules are present in the membrane; a cell might contain 9 or 10 different kinds of channels, chosen from many hundreds of channel proteins encoded in the genome. Perhaps surprisingly, the mathematical models predict that small changes in the balance among the different kinds of channels can lead to qualitatively dif ferent electrical behavior, for example converting a neuron that generates a simple rhythm into one that generates a complex syncopated beat.
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From page 87... ...
New generations of physical measurements that allow researchers to see directly the molecular events at synapses are probing the rules that underlie such continuous learning (Figure 4.5)
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From page 88... ...
When the cell generates an action potential, this can be monitored by an electrode placed in the cell body (red traces in b) , but the resulting electrical signals also are visible by measuring the intensity of second harmonics (black traces in b)
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From page 89... ...
Encouraged by the example of adaptation, a number of theoretical physicists have explored the problem of robustness in other biochemical networks. In the developing embryo, for example, one would like to know how it is possible for net works of genetic regulatory interactions to generate reproducible spatial structures despite inevitable variations in external conditions.
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From page 90... ...
As in other areas of physics, technically challenging, quantitative experiments are making precise our qualitative impressions of these phenomena, and this new experimental power provides fertile ground to test increasingly so phisticated theories. The breadth of this activity is enormous, from the dynamics of single molecules to perception and learning in the brain and from networks of biochemical reactions in single cells to the dynamics of evolution.
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