The mechanisms of pyknosis: hypercondensation and death

Intense nuclear condensation with intense refractivity (pyknosis) is the ubiquitous terminus of all apoptosis and some necrosis of vertebrate cells, but its structural basis is unknown. Intense condensations were induced in a model system, the avian erythrocyte, and three different molecular processes distinguished from each other. Two of the hypercondensations, nucleolytic pyknosis, as in mammalian apoptosis, and anucleolytic pyknosis, as in necrosis, appear to be energetically spontaneous and appear to have a conformational basis with the third hypercondensation being a trans-nuclear membrane osmotic pressure compression effect. Nucleolytic pyknosis as per apoptosis was not intrinsic in this system and required exogenous nuclease. The pure anucleolytic pyknosis supported by this system was not induced by the apoptopic induction agents, staurosporine or antitopoisomerases (I and II), indicating a simple but unusual signaling pathway for anucleolytic pyknosis. Molecular weight determinations of the H5, H3, H4, H2a, and H2b, with final errors of +/-1 Da or less, seem to eliminate histone modifications as the basis of anucleolytic pyknosis. The molecular basis of pyknosis is proposed to be from internucleosomal rotational angle freedom that permits internucleosomal sharing of basic histone tails of adjacent nucleosomes and nucleofilaments. Much of the favorable conformational energy of pyknosis may be from the entropy increase of tail delocalization.