Zsolt Mártonfalvi

• PhD
• Associate professor at Semmelweis University

A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500–1500 kDa. Using various structural-analysis methods, we in...

Titin is a multifunctional filamentous protein anchored in the M-band, a hexagonally organized supramolecular lattice in the middle of the muscle sarcomere. Functionally, the M-band is a framework that cross-links myosin thick filaments, organizes associated proteins, and maintains sarcomeric symmetry via its structural and putative mechanical prop...

The development of advanced experimental methodologies, such as optical tweezers, scanning-probe and super-resolved optical microscopies, has led to the evolution of single-molecule biophysics, a field of science that allows direct access to the mechanistic detail of biomolecular structure and function. The extension of single-molecule methods to t...

Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are generated and sensed in biological tissues. However, testing these mechanical hypotheses on proteins in their natural environment remains inaccesible to conventional tools. To address this limitation, here we demonstrate a mouse...

Abstract: Smooth-muscle titin (smitin) is a megadalton-size filamentous protein which is thought to play an important role in the structural organization of the contractile apparatus in smooth-muscle cells. The exact structure and interactions of smitin, however, are not fully known. In the present work we investigated the topological structure of...

Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces interact with titin in the sarcomere, enabling muscle contraction. However, testing these mechanical hypotheses on native titin in its natural environment has remained inaccessible to conventional genetics, biophysics and molecular b...

Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are generated and sensed in biological tissues. However, testing these mechanical hypotheses on native molecules in their natural environment remains inaccessible to conventional genetics, biophysics and molecular biology tools. To o...

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains. Accordingly, titin might provide a template that determines...

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the M-line the C-terminal region of titin overlaps with that of oppositely oriented titin from the other half of the sarcomere. Furthermore, titin-binding proteins such as myomesin and M-protein localize in the M-line so as to form a complex. The M-line complex appear...

The elasticity of muscle is principally determined by the I-band region of titin, consisting of 40-100 immunoglobulin-like (Ig) domains and two unstructured segments. Traditional force spectroscopy of titin can study only eight tandem Ig domains at a time, and the dominant entropic effect of the massive native titin polypeptide is lost. Here, we ha...

Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent f...

Titin, a giant, multi-domain filamentous protein has been suggested to act as a sensor of sarcomeric stress and strain. The exact mechanisms of this putative mechanosensing function are, however, yet unknown. To gain an insight into the mechanosensitive structural states we have manipulated titin with high-resolution optical tweezers and imaged str...

Titin molecules provide passive elasticity to muscle. As the sarcomeres are stretched, titin extends hierarchically according to the elasticity of its segments. Although extension is thought not to involve the unfolding of globular domains under physiological conditions, there is increasing evidence in support of such a possibility. While force-dri...

Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a parad...

The exclusion zone (EZ) is a boundary region devoid of macromolecules and microscopic particles formed spontaneously in the vicinity of hydrophilic surfaces. The exact mechanisms behind this remarkable phenomenon are still not fully understood and are debated. We measured the short- and long-time-scale kinetics of EZ formation around a Nafion gel e...

A simple, reliable and cost-effective fluidic channel, fabricated by using double-sided pressure-sensitive tapes, is demonstrated here. A laser-cutting method is applied to engrave structures in sheets of the tapes. After peeling off the tape liners, the structures could be easily integrated at room temperature with label-free optical waveguide bio...

Titin is a giant elastomeric protein responsible for the generation of passive muscle force. Mechanical force unfolds titin's globular domains, but the exact structure of the overstretched titin molecule is not known. Here we analyzed, by using high-resolution atomic force microscopy, the structure of titin molecules overstretched with receding men...

Titin, a giant elastomeric muscle protein has been implicated to function as a sensor of sarcomeric stress and strain but with unresolved mechanisms. To gain insight into titin's mechanosensory function here we manipulated single molecules with high-resolution optical tweezers. Discrete, stepwise transitions, with rates faster than canonical Ig-dom...

Contrary to the classical view, according to which all proteins adopt a specific folded conformation necessary for their function, intrinsically unstructured proteins (IUPs) display random-coil-like conformation under physiological conditions. We compared the structured and unstructured domains from titin, a giant protein responsible for striated-m...

Although Campbell and Lakie in a Comment to the Editor in this issue of Biophysical Journal suggested that exclusive cross-bridge action is behind muscle thixotropy, recent findings and our preliminary observations suggest that additional mechanisms could also be involved.

Titin is a giant protein that determines the elasticity of striated muscle and is thought to play important roles in numerous regulatory processes. Previous studies have shown that titin's PEVK domain interacts with F-actin, thereby creating viscous forces of unknown magnitude that may modulate muscle contraction. Here we measured, with optical twe...

The 39- to 42-residue-long amyloid beta-peptide (Abeta-peptide) forms filamentous structures in the neuritic plaques found in the neuropil of Alzheimer's disease patients. The assembly and deposition of Abeta-fibrils is one of the most important factors in the pathogenesis of this neurodegenerative disease. Although the structural analysis of amylo...

Amyloid fibrils are self-associating filamentous structures formed from the 39- to 42-residue-long amyloid beta peptide (Abeta peptide). The deposition of Abeta fibrils is one of the most important factors in the pathogenesis of Alzheimer's disease. Abeta25-35 is a fibril-forming peptide that is thought to represent the biologically active, toxic f...