Pluripotency Conversion of Gene Studied from Quantum Folding Theory

Abstract

The chemically and physically induced pluripotency in a stem cell is studied from the point of quantum transition between differentiation and pluripotency states in genes. The quantum folding theory of a macromolecule is briefly reviewed. The relation of protein folding rate with the number N of torsion modes participating in the quantum transition (coherence degree) is discussed and a simple statistical relationship is obtained. As a unifying approach to conformational quantum transition the folding rate formula can be generalized from protein to nucleic acid. It is found that the formula of folding rate versus N well fits RNA folding data. Then the quantum folding theory is applied to study the pluripotency conversion in stem cell. We proved that the acquisition of pluripotency is essentially a quantum-stochastic event of small-probability through the comparison of the rate with protein folding. Due to the large coherence degree of DNA and the uphill nature of torsion transition the pluripotency-acquisition rate should be small. By establishing the reaction network of the conformational change of the pluripotency genes the characteristic time of the chemical reprogramming is calculated and the result is consistent with experiments. The dependence of the transition rate on physical factors such as temperature, PH value and the volume and shape of the coherent domain of the gene is analyzed from the rate equation. Based on these studies an approach to the physically induced pluripotency with higher rate is proposed.