Periodic Reporting for period 1 - DNAGAM (DNA-guided self-organized active materials)
Berichtszeitraum: 2020-06-01 bis 2022-04-30
Molecular programs and active matter appear as two key ingredients for the emergence of shape in living systems. The former process chemical information, while the latter generates long-range mechanical forces. The coupling of these two elements is thus essential for the synthesis of life-like materials. This knowledge is employed for the development of life-like synthetic materials. However, the chemo-mechanical coupling in vitro remains challenging. A promising route for engineering such a coupling relies on stimuli-responsive synthetic hydrogels that change their macroscopic shape through a reorganization at the molecular level. This can be achieved by external chemical cues (as in shape-shifting DNA hydrogels) or internal force-generating systems (as in active gels). In this Marie Skłodowska Curie Action (MSCA), the Fellow aimed at the preparation of a first-ever synthetic biocompatible material that can mimic natural morphogenesis. Inspired by nature, such material was planned to be prepared by coupling of two essential processes: chemical reaction to produce morphogenetic substance; and mechanical forces for the shaping of the matter. The programmable production of the morphogen can be achieved by an out-of-equilibrium DNA-based chemical network which predictably generates single-stranded DNA morphogens. Combined with diffusion, the concentrations of the morphogen can be patterned with unique spatiotemporal precision, including travelling waves and stable fronts, which were pioneered by the host group. The autonomy of morphological structuring can be accomplished by linking the mechanical activity of active gels, composed of DNA-kinesins and microtubules, to the presence of the DNA morphogen. The latter acts as a cross-linker creating the clusters of kinesins and thus guiding the self-organization of the soft material by the collective action of nanoscale kinesin motor proteins which exert force on microtubules.
The formal objectives of the project are to (a) develop the mechanism of triggered activation of the motility of the active gel; (b) optimise out-of-equilibrium DNA-based reaction for the required experiment and (c) couple the production of the DNA morphogen with the microtubule/kinesin based active matter. Another goal of the project was to investigate the dependence of the concentration gradient of the kinesin motor protein on the motility of the microtubules.
The formal objectives of the project are to (a) develop the mechanism of triggered activation of the motility of the active gel; (b) optimise out-of-equilibrium DNA-based reaction for the required experiment and (c) couple the production of the DNA morphogen with the microtubule/kinesin based active matter. Another goal of the project was to investigate the dependence of the concentration gradient of the kinesin motor protein on the motility of the microtubules.
The objectives and goals have been addressed via four specific work packages: (1) Patterned self-organization of active matter on surfaces; (2) Self-organization of active gels and diffusion of DNA morphogens in them; (3) Synthetic morphogenesis from patterns generated by the reaction-diffusion mechanism; and (4) Synthesis of the covalent kinesin-DNA conjugate.
The Fellow developed DNA-responsive surfaces that were further used for the preparation of a new type of active matter that self-organizes over a centimetre scale. Active gels are capable of spontaneous motion and self-organization into a variety of patterns that, in some cases, induce flow and shape changes at the centimetre scale. To control the activity of such gels with a DNA signal, the Fellow exploited the approach based on the spatial separation of the gel's components that are brought together on demand by a specific DNA input. Furthermore, when the input DNA strand was heterogeneously distributed, it acted as a morphogen and determined pattern formation in the active gel depending on the DNA concentration gradient.
The impact of covalent kinesin-DNA conjugation could be a valuable contribution to the long-term advancements in the areas of synthetic morphogenesis and active matter. These conjugates could be obtained through the chemical modification of amino acids of kinesin.
The results of this project brought important insights into the manipulation of the microtubules' motility on the surface via DNA interactions. These include the complexity of DNA diffusion kinetics and the mechanics of microtubules’ motility in the presence of variable concentrations of kinesin. In addition, this work provides an approach allowing for the preparation of a synthetic material that actuates along a chemo-mechanical pathway.
According to the planned disseminations, the results were combined in the publication in a high-impact factor journal, as well as presented at a conference and a workshop.
The Fellow developed DNA-responsive surfaces that were further used for the preparation of a new type of active matter that self-organizes over a centimetre scale. Active gels are capable of spontaneous motion and self-organization into a variety of patterns that, in some cases, induce flow and shape changes at the centimetre scale. To control the activity of such gels with a DNA signal, the Fellow exploited the approach based on the spatial separation of the gel's components that are brought together on demand by a specific DNA input. Furthermore, when the input DNA strand was heterogeneously distributed, it acted as a morphogen and determined pattern formation in the active gel depending on the DNA concentration gradient.
The impact of covalent kinesin-DNA conjugation could be a valuable contribution to the long-term advancements in the areas of synthetic morphogenesis and active matter. These conjugates could be obtained through the chemical modification of amino acids of kinesin.
The results of this project brought important insights into the manipulation of the microtubules' motility on the surface via DNA interactions. These include the complexity of DNA diffusion kinetics and the mechanics of microtubules’ motility in the presence of variable concentrations of kinesin. In addition, this work provides an approach allowing for the preparation of a synthetic material that actuates along a chemo-mechanical pathway.
According to the planned disseminations, the results were combined in the publication in a high-impact factor journal, as well as presented at a conference and a workshop.
The proposed method for DNA-mediated activation of the active gels will provide a novel approach for the preparation of synthetic morphogenetic materials. Implementing the methodology results in enabled control over the motility of active matter and, most importantly, contributes to the field of life-mimicking materials, that have a significant scientific impact. The developed methodology could be further adapted by the research community and used for the development of more sophisticated materials. In addition, the expected long-term societal impact on a large group of people will be made by opening a new route to accessing novel self-fabricated, force-exerting synthetic soft matter with the potential of integration in soft robotics and biological environments that could be used in medicine.