Physical forces and non linear dynamics mould fractal cell shape: quantitative morphological parameters and cell phenotype.

Cell shape is mainly determined by biophysical constraints, interacting according to non-linear dynamics upon the basic units provided by the genome. In turn, the specific configuration a cell acquires plays a fundamental, permissive role in modulating gene expression and many other complex biological functions. Cell shape is tightly connected to cell activity and can be considered the most critical determinant of cell function. As a consequence, measurable parameters describing shape could be considered as 'omics' descriptors of the specific level of observation represented by the cell-stroma system. Such an approach promises to formalize some of the underlying basic mechanisms and, ultimately, provide a holistic understanding of the biological processes.

Quantitative shape analysis of chemoresistant colon cancer cells: correlation between morphotype and phenotype.

Morphological, qualitative observations allow pathologists to correlate the shape the cells acquire with the progressive, underlying neoplastic transformation they are experienced. Cell morphology, indeed, roughly scales with malignancy. A quantitative parameter for characterizing complex irregular structures is the Normalized Bending Energy (NBE). NBE provides a global feature for shape characterization correspondent to the amount of energy needed to transform the specific shape under analysis into its lowest energy state. We hypothesized that a chemotherapy resistant cancer cell line would experience a significant change in its shape, and that such a modification might be quantified by means of NBE parameterization. We checked out the usefulness of a mathematical algorithm to distinguish wild and 5-fluorouracil (5-FU)-resistant colon cancer HCT-8 cells (HCT-8FUres). NBE values, as well as cellular and molecular parameters, were recorded in both cell populations. Results demonstrated that acquisition of drug resistance is accompanied by statistically significant morphological changes in cell membrane, as well as in biological parameters. Namely, NBE increased progressively meanwhile cells become more resistant to increasing 5-FU concentrations. These data indicate how tight the relationships between morphology and phenotype is, and they support the idea to follow a cell transition toward a drug-resistant phenotype by means of morphological monitoring.

Embryonic morphogenetic field induces phenotypic reversion in cancer cells. Review article.

Cancer cells introduced into developing embryos can be committed to a complete reversion of their malignant phenotype. It is unlikely that such effects could be ascribed to only few molecular components interacting according to a simple linear-dynamics model, and they claim against the somatic mutation theory of cancer. Some 50 years ago, Needham and Waddington speculated that cancer represents an escape from morphogenetic field like those which guide embryonic development. Indeed, disruption of the morphogenetic field of a tissue can promote the onset as well as the progression of cancer. On the other hand, placing tumor cells into a "normal" morphogenetic field - like that of an embryonic tissue - one can reverse malignant phenotype, "reprogramming" tumor into normal cells. According to the theoretical framework provided by the thermodynamics of dissipative systems, morphogenetic fields could be considered as distinct attractors, to which cell behaviors are converging. Cancer-attractors are likely positioned somewhat close to embryonic-attractors. Indeed, tumors share several morphological and ultra-structural features with embryonic cells. The recovering of an "embryonic-like" cell shape might enable the gene regulatory network to reactivate embryonic programs, and consequently to express antigenic and biochemical embryonic characters. This condition confers to cancer an unusual sensitivity to embryonic regulatory cues. Thus, it is not surprising that cancer cells exposed to specific embryonic morphogenetic fields undergoes significant modifications, eventually leading to a complete phenotypic reversion.