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Relevance of Single Cell and Single Molecule Studies at Different Biological and Physical Length Scales

Author(s): Wenfa Ng

Scale transcends multiple levels of biological and physical organization and is the critical factor that determines success of any scientific investigation. Specifically, the scale at which a question is posed plays a crucial role in influencing the type of experiments and apparatuses needed. Single cell and single molecule experiments came to the fore of experiment science due to its capability at addressing a fundamental problem in biology and physical science: does the same behaviour in cells and molecules transcend different length and population scales? Thus far, single cell experiments could be achieved with trapping of single cell using optical tweezer traps and microfluidic channels. The same, however, is not true for single molecule studies, which remains in the realm of theoretical and simulation studies. Specifically, single molecule experiment remains at the hundreds to thousands of molecules level, where possible skew in the population of molecules sampled could provide a false depiction of molecular reality of a larger population. But what do scientists learn from single cell and single molecule studies? Is it the uncovering of mysteries of the probabilistic behaviour at the single entity level, guided by perhaps quantum mechanics? The answer is no for single cell studies, given that cellular decision making require the input of tens to hundreds of molecular sensors and effectors within a cell. Hence, single cell behaviour is not random, but directed at a nutrient or concentration gradient or signalling source. On the other hand, enzymatic catalysis of a single molecule substrate with the active site involves a quantum mechanical crosstalk. Thus, reaction between the substrate molecule and the active site of an enzyme proceeds if suitable energy levels (i.e., quantum mechanical states) are found for both parties. Given that distribution of quantum mechanical states is probabilistic, stochasticity rules single molecule interaction such as a covalent bond formation reaction between reactant A and B. Thus, single cell and single molecule studies do hold relevance in biological and physical sciences research if the correct experiment tool is used for a pertinent question at an appropriate length and population scale. For example, while tremendous amount of basic understanding could be derived from single cell experiments, single cell perspective is not relevant to questions examining the interactions between two large subpopulations of cells. Single molecule experiments, on the other hand, remains in the theoretical and simulation realm for highlighting the effect of quantum mechanics in guiding the behaviour of molecules at the nanoscale.

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