Randomness in microtubule dynamics: an error that requires correction or an inherent plasticity required for normal cellular function?

Abstract

Microtubules (MTs) play roles in regulating the mechanical structure and dynamics of cells. While MTs appear to be highly ordered structures, recent data suggest some randomness in their structure and dynamics. Part of this inherent randomness is attributed to errors and correction mechanisms are being investigated to overcome these ‘mistakes.’ However, this randomness may also be part of the normal intracellular function of MTs. It is possible that random events in MT structure and dynamics may contribute to their normal function and may even be part of an improved efficacy mechanism. An alternative view, wherein MT and kinetochore errors are part of required cell plasticity, is also discussed. These data may further support the concept of randomness in biological pathways as part of self‐organization or accurate and enhanced function.

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

“…Variability is a characteristic of many biological systems and is also seen in the compensatory effects toward chronic medications. 38 , 39 , 40 The unpredictable response to drugs remains a major challenge for designing effective therapeutic regimens. The variability in compensatory pathways may impact the clinical efficacy of chronic drug administration.…”

“…Marked variability is a characteristic of many intracellular processes. 39 , 40 , 57 , 58 Drug-target interactions in the microenvironment of the cell do not always follow the rules of simple diffusion and chemical reactions. Multiple non-specific interactions of drugs with macromolecules in cells are not measured by simple pharmacodynamics methods.…”

“… 59 Many of the functions of the microtubules manifest as distinct variability patterns. 39 , 60 Ongoing dynamic changes in the strength of synaptic connections in excitatory neurons occur when calcium ions Ca 2+ bind the Ca 2+ sensor, calmodulin (CaM), thus contributing to synaptic plasticity. Modeling the activation of downstream Ca 2+ /CaM-dependent binding proteins has shown that the model output is robust to parameter variability.…”

Order Through Disorder: The Characteristic Variability of Systems

“…Variability in biological systems can be viewed as a contributing modality of their function (Clarke and Crame, 2010;Farahpour et al, 2018). Randomness can be considered as a property of causal processes, contributing to complex system function (Ilan, 2019e;Kenig and Ilan, 2019;Khoury and Ilan, 2019). Random genetic drift is accepted as the random fluctuations in the numbers of gene variants in a population (Lynch et al, 2016).…”

Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy

“…[144][145][146] The dynamic instability of MTs exemplifies the variability in their structure and function. 147 Variability contributes to cell plasticity and is a method used for overcoming errors in the assembly and tasks at the cellular and potentially whole organ levels. 145,145,146,[148][149][150] Variability also characterizes the response to certain therapies.…”