Biology subjects

Arampatzis, A.

Publications and source records attributed to Arampatzis, A..

11 recordsLinked to original sources

bioRxiv2026

Engineering Cybergenetic Cell-Based Therapies

Adaptive, closed-loop control of cellular behavior is essential for next-generation therapies, yet most current treatments operate in an open-loop manner and lack robustness to patient variability and disease dynamics. Here, we establish a controltheoretic platform for rational engineering of closed-loop cell-based therapies that achieve precise and robust regulation. First, we introduce multi-dimensional nullgram profiling, a high-throughput approach that enables quantitative prediction and design of advanced genetic controllers in human cells across circuit topologies and parameter regimes in a single experiment. To evaluate dynamic therapeutic behavior, we next develop Cyberpatient-in-the-loop, an optogenetic digital twin platform that interfaces engineered mammalian cells with computational disease models, enabling systematic testing of closed-loop performance under realistic perturbations. Finally, we leverage these approaches to implement integral feedback cell therapies that sense inflammatory signals and autonomously regulate cytokine levels in primary immune cell cultures. Together, these results establish a general paradigm for engineering cellbased control systems and provide a foundation for next-generation cell therapies.

synthetic biology↗

bioRxiv2023

Spatiotemporal modulation of a fixed set of muscle synergies during unpredictable and predictable gait perturbations in older adults

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed and the recovery steps. Sixty-three healthy older adults (71.2 {+/-} 5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (p<0.05). These modifications were observed up to four recovery steps and were more pronounced (p<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may facilitate the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations. Summary statementThe flexible recruitment of the four and well-known muscle synergies responsible for unperturbed walking during unpredictable and predictable gait perturbations indicates an effective way to counteract locomotor perturbations, where fast reactive responses are necessary to maintain postural stability.

neuroscience↗

bioRxiv2023

Speed-specific optimal contractile conditions of the human soleus muscle from slow to maximum running speed

The soleus is the main muscle for propulsion during human running but its operating behavior across the spectrum of physiological running speed is currently unknown. This study investigated experimentally the soleus muscle activation patterns and contractile conditions for force generation, power production and efficient work production (i.e. force-length potential, force-velocity potential, power-velocity potential and enthalpy efficiency) at seven running speeds (3.0 m/s to individual maximum). During submaximal running (3.0 to 6.0 m/s), the soleus fascicles shortened close to optimal length and at a velocity close to the efficiency-maximum, two contractile conditions for economical work production. At higher running speeds (7.0 m/s to maximum), the soleus muscle fascicles still operated near optimum length, yet the fascicle shortening velocity increased and shifted towards the optimum for mechanical power production with a simultaneous increase in muscle activation, providing evidence for three cumulative mechanisms to enhance mechanical power production. Using the experimentally-determined force-length-velocity potentials and muscle activation as inputs in a Hill-type muscle model, a reduction in maximum soleus muscle force at speeds [≥]7.0 m/s and a continuous increase in maximum mechanical power with speed was predicted. The reduction in soleus maximum force was associated with a reduced force-velocity potential. The increase in maximum power was explained by an enhancement of muscle activation and contractile conditions until 7.0 m/s, yet at the maximal running speed mainly by increased muscle activation. Summary statementThe study provides experimental evidence that the human soleus muscle favors contractile conditions for economical work production during submaximal running and for enhancing mechanical power production during maximal running speed.

physiology↗

bioRxiv2022

Contractile work and biarticular mechanisms of the triceps surae muscles facilitate net ankle mechanical work at high walking speeds

Increasing walking speed is accompanied by an enhancement of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential. We measured Achilles tendon (AT) elongation and, based on an experimentally determined AT-force-elongation relationship; we quantified AT-force as a proxy of the triceps surae muscle force at four walking speeds (slow 0.7 m.s-1, preferred 1.4 m.s-1, transition 2.0 m.s-1 and maximum 2.6{+/-}0.3 m.s-1). Further, we investigated the mechanical power and work of the triceps surae muscles at the ankle joint (TSA) and the mechanical power and work of the biarticular gastrocnemii at the ankle and knee joint. We found a ~21% decrease of maximum AT-force at the two higher speeds compared to the preferred; however, the net TSA-work increased as a function of walking speed. An earlier plantarflexion accompanied by increased activation of the triceps surae muscles and a knee-to-ankle energy transfer via the biarticular gastrocnemii enhanced the net TSA-mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speeds, respectively. Our findings provide first time evidence for different mechanistic participation of the monoarticular soleus muscle and the biarticular gastrocnemii for the speed-related enhancement of net TSA-work.

bioengineering↗

bioRxiv2021

Sex-specific tuning of modular muscle activation patterns for locomotion in young and older adults

There is increasing evidence that including sex as a biological variable is of crucial importance to promote rigorous, repeatable and reproducible science. In spite of this, the body of literature that accounts for the sex of participants in human locomotion studies is small and often produces controversial results. Here, we investigated the modular organization of muscle activation patterns for human locomotion using the concept of muscle synergies with a double purpose: i) uncover possible sex-specific characteristics of motor control and ii) assess whether these are maintained in older age. We recorded electromyographic activities from 13 ipsilateral muscles of the lower limb in young and older adults of both sexes walking (young and old) and running (young) on a treadmill. The data set obtained from the 215 participants was elaborated through non-negative matrix factorization to extract the time-independent (i.e., motor modules) and time-dependent (i.e., motor primitives) coefficients of muscle synergies. We found sparse sex-specific modulations of motor control. Motor modules showed a different contribution of hip extensors, knee extensors and foot dorsiflexors in various synergies. Motor primitives were wider (i.e., lasted longer) in males in the propulsion synergy for walking (but only in young and not in older adults) and in the weight acceptance synergy for running. Moreover, the complexity of motor primitives was similar in younger adults of both sexes, but lower in older females as compared to older males. In essence, our results revealed the existence of small but defined sex-specific differences in the way humans control locomotion and that these strategies are not entirely maintained in older age.

neuroscience↗

bioRxiv2021

Muscle-specific economy of force generation and efficiency of work production during human running

Human running features a spring-like interaction of body and ground, enabled by elastic tendons that store mechanical energy and facilitate muscle operating conditions to minimize the metabolic cost. By experimentally assessing the operating conditions of two important muscles for running, the soleus and vastus lateralis, we investigated physiological mechanisms of muscle energy production and muscle force generation. Results showed that the soleus continuously shortened throughout the stance phase, operating as energy generator under conditions that were found to be optimal for work production: high force-length potential and enthalpy efficiency. The vastus lateralis promoted tendon energy storage and contracted nearly isometrically close to optimal length, resulting in a high force-length-velocity potential beneficial for economical force generation. The favorable operating conditions of both muscles were a result of an effective length and velocity-decoupling of fascicles and muscle-tendon unit mostly due to tendon compliance and, in the soleus, marginally by fascicle rotation.

biophysics↗

bioRxiv2020

Quantifying mechanical loading and elastic strain energy of the human Achilles tendon during walking and running

The purpose of the current study was to assess Achilles tendon (AT) mechanical loading and strain energy during locomotion using a new in vivo approach for measuring AT length that considers the AT curve-path shape. Eleven participants walked at 1.4 m/s and ran at 2.5 m/s and 3.5 m/s on a treadmill. AT length, defined as the distance between its origin at the gastrocnemius medialis myotendinous junction (MTJ) and the calcaneal insertion, was determined experimentally by integrating kinematics and ultrasound analysis. Small foil markers were placed on the skin covering the AT path from the origin to the insertion, and the MTJ, tracked using ultrasonography, was projected to the reconstructed skin to account for their misalignment. Skin-to-bone displacements were assessed during a passive rotation (5 {degrees}/s) of the ankle joint and considered in the calculation of AT length. Force and strain energy of the AT during locomotion were calculated by fitting a quadratic function to the experimentally measured tendon force-length curve obtained from maximum voluntary isometric contractions. Maximum AT strain and force were affected by speed (p<0.05, ranging from 4.0 to 4.9% strain and 1.989 to 2.556 kN), yet insufficient in magnitude to be considered an effective stimulus for tendon adaptation. Further, we found a recoil of elastic strain energy at the beginning of the stance phase of running (70-77 ms after touch down) between 1.7 {+/-}0.6 and 1.9 {+/-}1.1 J, which might be functionally relevant for running efficiency. Summary statementA new accurate in vivo approach to assess Achilles tendon strain, force and strain energy during locomotion.

bioengineering↗

bioRxiv2020

Muscle activation patterns are more constrained and regular in treadmill than in overground human locomotion

The use of motorized treadmills as convenient tools for the study of locomotion has been in vogue for many decades. However, despite the widespread presence of these devices in many scientific and clinical environments, a full consensus on their validity to faithfully substitute free overground locomotion is still missing. Specifically, little information is available on whether and how the neural control of movement is affected when humans walk and run on a treadmill as compared to overground. Here, we made use of linear and nonlinear analysis tools to extract information from electromyographic recordings during walking and running overground, and on an instrumented treadmill. We extracted synergistic activation patterns from the muscles of the lower limb via non-negative matrix factorization. We then investigated how the motor modules (or time-invariant muscle weightings) were used in the two locomotion environments. Subsequently, we examined the timing of motor primitives (or time-dependent coefficients of muscle synergies) by calculating their duration, the time of main activation, and their Hurst exponent, a nonlinear metric derived from fractal analysis. We found that motor modules were not influenced by the locomotion environment, while motor primitives resulted overall more regular in treadmill than in overground locomotion, with the main activity of the primitive for propulsion shifted earlier in time. Our results suggest that the spatial and sensory constraints imposed by the treadmill environment forced the central nervous system to adopt a different neural control strategy than that used for free overground locomotion. A data-driven indication that treadmills induce perturbations to the neural control of locomotion.

neuroscience↗

bioRxiv2020

Lower complexity of motor primitives ensures robust control of high-speed human locomotion

Walking and running are mechanically and energetically different locomotion modes. For selecting one or another, speed is a parameter of paramount importance. Yet, both are likely controlled by similar low-dimensional neuronal networks that reflect in patterned muscle activations called muscle synergies. Here, we investigated how humans synergistically activate muscles during locomotion at different submaximal and maximal speeds. We analysed the duration and complexity (or irregularity) over time of motor primitives, the temporal components of muscle synergies. We found that the challenge imposed by controlling high-speed locomotion forces the central nervous system to produce muscle activation patterns that are wider and less complex relative to the duration of the gait cycle. The motor modules, or time-independent coefficients, were redistributed as locomotion speed changed. These outcomes show that robust locomotion control at challenging speeds is achieved by modulating the relative contribution of muscle activations and producing less complex and wider control signals, whereas slow speeds allow for more irregular control.

neuroscience↗

bioRxiv2019

Humans exploit robust locomotion by improving the stability of control signals

Is the control of movement less stable when we walk or run in challenging settings? One might intuitively answer affirmatively, given that adding constraints to locomotion (e.g. rough terrain, age-related impairments, etc.) imply less stable movements. We investigated how young and old humans synergistically activate muscles during locomotion, when different perturbation levels are introduced. Of these control signals, called muscle synergies, we then analyzed the stability over time. Surprisingly, we found that perturbations and older age force the central nervous system to produce more stable signals. These outcomes show that robust locomotion in challenging settings is achieved by increasing the stability of control signals, whereas easier tasks allow for more unstable control.

neuroscience↗

bioRxiv2018

Modular organization of the murine locomotor pattern in presence and absence of sensory feedback from muscle spindles

For exploiting terrestrial and aquatic locomotion, vertebrates must build their locomotor patterns based on an enormous amount of variables. The great number of muscles and joints, together with the constant need for sensory feedback information (e.g. proprioception), make the task of creating and controlling movement a problem with overabundant degrees of freedom. It is widely accepted that the central nervous system might simplify the creation and control of movement. This could happen through the generation of activation patterns, which are common to many different muscles, rather than specific to individual muscles. These activation patterns, called muscle synergies, can be extracted from electromyographic data and describe the modular organization of movement. We extracted muscle synergies from the hindlimb muscle activities of wild type and genetically modified mice, in which sensory feedback from muscle spindles is eliminated. Muscle spindle-deficient mice underwent a modification of the temporal structure (motor primitives) of muscle synergies that resulted in diminished functionality during walking. In addition, both the temporal and spatial components (motor modules) of muscle synergies were severely affected when external perturbations were introduced of when animals were immersed in water. These findings show that group Ia/II sensory feedback from muscle spindles regulates motor function in normal and perturbed walking. Moreover, when group Ib Golgi tendon organ feedback is lacking due to the reduction of gravitational load in conditions of enhanced buoyancy, the modular organization of swimming is almost completely compromised.\n\nSignificance statementLocomotion on land and in water requires the coordination of a great number of muscle activations and joint movements. Moreover, constant feedback about the position of own body parts in relation to the surrounding environment and the body itself (proprioception) is required to maintain stability and avoid failure. The theory of muscle synergies states that the central nervous system might control muscles in orchestrated groups (synergies) rather than individually. We used this concept on genetically modified mice, lacking one of the two classes of proprioceptors. Our results provide evidence that proprioceptive feedback is required by the central nervous system to accurately tune the modular organization of locomotion.

neuroscience↗