scholarly journals Membrane-confined liquid-liquid phase separation toward artificial organelles

2021 ◽  
Vol 7 (22) ◽  
pp. eabf9000
Author(s):  
Wenjing Mu ◽  
Zhen Ji ◽  
Musen Zhou ◽  
Jianzhong Wu ◽  
Yiyang Lin ◽  
...  

As the basic unit of life, cells are compartmentalized microreactors with molecularly crowded microenvironments. The quest to understand the cell origin inspires the design of synthetic analogs to mimic their functionality and structural complexity. In this work, we integrate membraneless coacervate microdroplets, a prototype of artificial organelles, into a proteinosome to build hierarchical protocells that may serve as a more realistic model of cellular organization. The protocell subcompartments can sense extracellular signals, take actions in response to these stimuli, and adapt their physicochemical behaviors. The tiered protocells are also capable of enriching biomolecular reactants within the confined organelles, thereby accelerating enzymatic reactions. The ability of signal processing inside protocells allows us to design the Boolean logic gates (NOR and NAND) using biochemical inputs. Our results highlight possible exploration of protocell-community signaling and render a flexible synthetic platform to study complex metabolic reaction networks and embodied chemical computation.

2020 ◽  
Vol 6 (6) ◽  
pp. 245-255
Author(s):  
Fang Pu ◽  
Jinsong Ren ◽  
Xiaogang Qu

AbstractNanozymes, nanomaterials with enzyme-like activity, have been considered as promising alternatives of natural enzymes. Molecular logic gates, which can simulate the function of the basic unit of an electronic computer, perform Boolean logic operation in response to chemical, biological, or optical signals. Recently, the combination of nanozymes and logic gates enabled bioinformation processing in a logically controllable way. In the review, recent progress in the construction of nanozyme-based logic gates integrated with their utility in sensing is introduced. Furthermore, the issues and challenges in the construction processes are discussed. It is expected the review will facilitate a comprehensive understanding of nanozyme-based logic systems.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charles El Helou ◽  
Philip R. Buskohl ◽  
Christopher E. Tabor ◽  
Ryan L. Harne

AbstractIntegrated circuits utilize networked logic gates to compute Boolean logic operations that are the foundation of modern computation and electronics. With the emergence of flexible electronic materials and devices, an opportunity exists to formulate digital logic from compliant, conductive materials. Here, we introduce a general method of leveraging cellular, mechanical metamaterials composed of conductive polymers to realize all digital logic gates and gate assemblies. We establish a method for applying conductive polymer networks to metamaterial constituents and correlate mechanical buckling modes with network connectivity. With this foundation, each of the conventional logic gates is realized in an equivalent mechanical metamaterial, leading to soft, conductive matter that thinks about applied mechanical stress. These findings may advance the growing fields of soft robotics and smart mechanical matter, and may be leveraged across length scales and physics.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4785
Author(s):  
Enrico Kittel-Boselli ◽  
Karla Elizabeth González Soto ◽  
Liliana Rodrigues Loureiro ◽  
Anja Hoffmann ◽  
Ralf Bergmann ◽  
...  

Clinical translation of novel immunotherapeutic strategies such as chimeric antigen receptor (CAR) T-cells in acute myeloid leukemia (AML) is still at an early stage. Major challenges include immune escape and disease relapse demanding for further improvements in CAR design. To overcome such hurdles, we have invented the switchable, flexible and programmable adaptor Reverse (Rev) CAR platform. This consists of T-cells engineered with RevCARs that are primarily inactive as they express an extracellular short peptide epitope incapable of recognizing surface antigens. RevCAR T-cells can be redirected to tumor antigens and controlled by bispecific antibodies cross-linking RevCAR T- and tumor cells resulting in tumor lysis. Remarkably, the RevCAR platform enables combinatorial tumor targeting following Boolean logic gates. We herein show for the first time the applicability of the RevCAR platform to target myeloid malignancies like AML. Applying in vitro and in vivo models, we have proven that AML cell lines as well as patient-derived AML blasts were efficiently killed by redirected RevCAR T-cells targeting CD33 and CD123 in a flexible manner. Furthermore, by targeting both antigens, a Boolean AND gate logic targeting could be achieved using the RevCAR platform. These accomplishments pave the way towards an improved and personalized immunotherapy for AML patients.


2021 ◽  
Vol 48 (2) ◽  
pp. 177-191
Author(s):  
Martin Frické

The article describes and explains Boolean logic (or Boolean algebra) in its two principal forms: that of truth-values and the Boolean connectives and, or, and not, and that of set membership and the set operations of intersection, union and complement. The main application areas of Boolean logic to know­ledge organization, namely post-coordinate indexing and search, are introduced and discussed. Some wider application areas are briefly mentioned, such as: propositional logic, the Shannon-style approach to electrical switching and logic gates, computer programming languages, probability theory, and database queries. An analysis is offered of shortcomings that Boolean logic has in terms of potential uses in know­ledge organization.


Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 984 ◽  
Author(s):  
Victoria Goldsworthy ◽  
Geneva LaForce ◽  
Seth Abels ◽  
Emil Khisamutdinov

RNA aptamers that bind non-fluorescent dyes and activate their fluorescence are highly sensitive, nonperturbing, and convenient probes in the field of synthetic biology. These RNA molecules, referred to as light-up aptamers, operate as molecular nanoswitches that alter folding and fluorescence function in response to ligand binding, which is important in biosensing and molecular computing. Herein, we demonstrate a conceptually new generation of smart RNA nano-devices based on malachite green (MG)-binding RNA aptamer, which fluorescence output controlled by addition of short DNA oligonucleotides inputs. Four types of RNA switches possessing AND, OR, NAND, and NOR Boolean logic functions were created in modular form, allowing MG dye binding affinity to be changed by altering 3D conformation of the RNA aptamer. It is essential to develop higher-level logic circuits for the production of multi-task nanodevices for data processing, typically requiring combinatorial logic gates. Therefore, we further designed and synthetized higher-level half adder logic circuit by “in parallel” integration of two logic gates XOR and AND within a single RNA nanoparticle. The design utilizes fluorescence emissions from two different RNA aptamers: MG-binding RNA aptamer (AND gate) and Broccoli RNA aptamer that binds DFHBI dye (XOR gate). All computationally designed RNA devices were synthesized and experimentally tested in vitro. The ability to design smart nanodevices based on RNA binding aptamers offers a new route to engineer “label-free” ligand-sensing regulatory circuits, nucleic acid detection systems, and gene control elements.


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