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A sense of direction: follow the chemical trail

Biophysicists at Yale stimulate single living cells with light and microparticles.
Biophysicists at Yale stimulate single living cells with light and microparticles.
Science Daily (Credit: Holger Kress and Eric Dufresne).

I don't always express myself on the surface, but I'm looking for a signal that you appreciate my complexity. Send me the right message that will penetrate my membranes, turn on my protein expression and release my potential energy. (  —Author Unknown.

In a highly organized, multi-faceted process, prokaryotic and eukaryotic cells have both developed many kinds of biochemical strategies to determine direction and to respond to external cues. This movement is an essential part of the active locomotion of cells or cell migration and integral to many eukaryotic activities including immune response, neuronal activation, embryogenesis, and the progression of various diseases such as cancer and atherosclerosis. Among the several categories of cell migration, and the focus of this article, is chemotaxis, a term that describes migration based on “sensing” chemicals in the cellular environment.

Chemotaxis can be either in the direction toward or away from chemical signals. To accomplish their critical functions, cells make use of specific chemical gradients usually in the area surrounding a target. While many of the molecular components have been identified, the exact details and mechanisms of how the signaling circuits are coordinated within and among individual cells have yet to be worked out.

A particularly useful model to explore directed cell migration in response to chemical signals is the human neutrophil. Neutrophils, also known as polymorphonuclear leukocytes (PMNs), are a major type of white blood cells, crucial in host defense against bacterial infections and the fastest moving mammalian cells known. Chemotaxis allows neutrophils to move quickly to the site of infection and destroy the pathogens. As the immune cells orient along a chemical concentration gradient, a complex series of events occurs leading to chemotaxis: reorganization of actin filaments, changes in shape, the establishment of polarity, and reversible attachment.

The neutrophil model system was advanced by the development of an immortal cell line that can be propagated in culture and stored long-term in frozen aliquots. The cell line permits the study of cell migration without having to isolate neutrophils from primary tissue, such as bone marrow or peripheral blood. From the human promyelocytic leukemia (HL-60) cell line, neutrophil-like cells can be derived using agents that induce differentiation.

Recently, bioengineers at Yale University, led by Holger Kress and Eric Dufresne, designed a technique so that micro-particles mimicking bacteria are manipulated via a highly focused laser beam (optical tweezers). The new approach, combining optical and materials science, is an effort to examine how immune cells process chemical signals. Like bacteria, the sponge-like microparticles created in the laboratory of Tarek Fahmy, also at Yale, slowly secrete molecules, leaving behind chemical trails as they move.

The team of scientists could control the movements of neutrophils by moving the microparticles as well as the pattern of chemicals released with directed beams of light. Videos produced by the researchers show the neutrophils moving toward or away from the microparticles depending on the chemical stimulus emitted. They were also able to study how the neutrophils responded to opposing signals sent by several artificial bacteria. The significance of the study is that the researchers demonstrate that optical tweezers can be used to control chemical gradients, not just physical objects. More important, the technique could provide a way for scientists to investigate how many different cell types, such as brain cells and cancer cells network, spread, or develop in response to environmental cues.

References and Read-More-About-It:
1. Kress H, Park JG, Mejean CO et al. Cell stimulation with optically manipulated microsources. Nat Methods. 2009 Dec;6(12):905-9. Epub 2009 Nov 15.
2. ScienceDaily. Retrieved April 19, 2010, from­ /releases/2010/03/100329203222.htm
3. Millius A, Weiner OD. Chemotaxis in neutrophil-like HL-60 cells. Methods Mol Biol. 2009;571:167-77.
4. Niggli V. Signaling to migration in neutrophils: importance of localized pathways. Int J Biochem Cell Biol. 2003 Dec;35(12):1619-38.
5. Mejean CO, Schaefer AW, Millman EA et al. Multiplexed force measurements on live cells with holographic optical tweezers. Opt Express. 2009 Apr 13;17(8):6209-17.



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