Publications

The present work shows that E-hook fragments possess functional structural differences governed by electrostatic interactions and sequence composition. The acidic C-terminal tails of tubulin, known as E-hooks, play a central role in regulating interactions between microtubules and motor proteins, microtubule-associated proteins, and enzymatic modifiers. Despite their functional importance, the intrinsic structural properties of these peptide segments remain poorly characterized due to their intrinsically disordered nature. In this work, we present quantum-mechanically optimized structures of hexamer peptides derived from β-tubulin E-hook sequences. Density functional theory calculations were used to optimize peptide geometries using progressively larger basis sets. From the optimized geometries, we calculated theoretical Raman spectra, Ramachandran backbone dihedral distributions, and measured radii of gyration to resolve composition-dependent structural tendencies. The combined Raman and conformational analyses provide a systematic computational approach for comparing simulated and experimental Raman spectra of tubulin E-hooks and other intrinsically disordered proteins and offer insight into how E-hooks contribute to the recognition mechanisms underlying the tubulin code.

This present work shows that E-hook fragments possess functional structure differences governed by electrostatic interactions and sequence composition. The acidic C-terminal tails of tubulin, known as E-hooks, play a central role in regulating interactions between microtubules and motor proteins, microtubule-associated proteins, and enzymatic modifiers. Despite their functional importance, the intrinsic structural properties of these peptide segments remain poorly characterized due to their intrinsically disordered nature. In this work, we present quantum-mechanically optimized structures of hexamer peptides derived from β-tubulin E-hook sequences. Density functional theory calculations were used to optimize peptide geometries using progressively larger basis sets. From the optimized geometries we calculated theoretical Raman spectra, Ramachandran backbone dihedral distributions, and measured radii of gyration to resolve composition dependent structural tendencies. The combined Raman and conformational analyses provide a systematic computational approach for comparing simulated and experimental Raman spectra of tubulin E-hooks and other intrinsically disordered proteins and offer insight into how E-hooks contribute to the recognition mechanisms underlying the tubulin code.

Mechanical cues from the cellular microenvironment are key regulators of cytoskeletal organization, force generation, and mechanotransduction, yet defining how specific mechanical inputs control distinct cytoskeletal processes remains an ongoing challenge. Mechanically tunable microenvironments have become essential tools for addressing this problem by enabling systematic variation of substrate stiffness, viscoelasticity, and interfacial mechanics under well-controlled conditions. In this review, we survey major classes of tunable platforms used to study cytoskeletal dynamics, including biologically derived matrices, synthetic hydrogels, micropatterned and nanotopographic substrates, and polymeric thin films, highlighting how each approach affords unique insight into cytoskeletal regulation. Beyond material composition, these platforms reveal key mechanistic principles: they allow separation of protrusion, contractility, and adhesion processes; uncover how mechanical coupling drives alignment and polarity; and identify stiffness thresholds that govern force transmission. Control over interface mechanics also enables selective engagement of cytoskeletal modules that are otherwise inseparable on rigid substrates. We conclude by discussing current limitations and emerging opportunities for integrating tunable microenvironments with quantitative measurements of force generation and cytoskeletal organization, advancing a more predictive understanding of how cells sense, transmit, and respond to mechanical information.