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Lighting Up the Mechanome--Matthew J. Lang
Pages 39-48

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From page 39...
... Malaria, which infects 500 million people and causes 2 million deaths each year, works through a number of mechanical processes, including parasite invasion of red blood cells (RBCs) , increased RBC adhesions, and overall stiffening of RBCs.
From page 40...
... Intracellular changes in cancerous cells bring about cell growth and proliferation, cell motility, and migration. These processes are currently targeted by Taxol, a potent chemotherapy drug that impedes the progression of cancer by stabilizing microtubules in a polymerized state, thus shutting down the machinery of cell division.
From page 41...
... end of microtubules. In some cases, such as the kinesins that carry vesicles containing neurotransmitters along the sciatic nerve axon, this progress takes place over the length scale of about a meter and is a critical mechanism for cargo delivery. The design of biological motors can be classified by cataloging the motor's general structural features, fuel type, stepping distance, stall force, and other mechanical parameters.
From page 42...
... Highly tuned control over these forces and structures is orchestrated through mechanical and biochemical signals that initiate and terminate motility cycles. Mechanotransduction, a critical aspect of control, refers to the process whereby cells actively respond to mechanical signals through changes in morphology, signaling, and biochemical response.
From page 43...
... For example, mesenchymal stem cells grown on a matrix with elasticity resembling that of tissues such as 1 kPa brain, 10 kPa muscle, and 100 kPa bone differentiate into cells resembling neurons, muscles, and osteoblasts, respectively (Engler et al., 2006) . The external environment of a cell contains many organized mechanical structures.
From page 44...
... Measurements at the Molecular Level With the advanced instrumentation and experimental methods described below, we are poised to measure the mechanome at the molecular level. For example, force microscopy, in which controlled loads are applied to structures while they are tracked with nanometer-level resolution, can be used to measure mechanical transitions in unfolding protein structures, the rupture of individual molecular interactions, and the motility of biological motors.
From page 45...
... Molecular biology strategies, such as the encodeable green fluorescence protein (GFP) , which can genetically label proteins, have advanced the field, as have new probes, such as enhanced organic dyes and quantum dots, which have enabled observations of single molecules over extended periods of time.
From page 46...
... The middle frame shows how force on the hairpin is repeatedly transitioned from low to high with hairpin opening occurring at approximately ~18pN. The lower frame shows photon counts with donor (upper)
From page 47...
... 2006. Matrix elasticity directs stem cell lineage specification.


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