Biomedical subjects

Gabor Forgacs

Publications and source records attributed to Gabor Forgacs.

6 recordsLinked to original sources

PubMed2004

Role of the cytoskeleton in signaling networks.

Intracellular signal transduction occurs through cascades of reactions involving dozens of proteins that transmit signals from the cell surface, through a crowded cellular environment filled with organelles and a filamentous cytoskeleton, to specific targets. Numerous signaling molecules are immobilized or transiently bound to the cytoskeleton, yet most models for signaling pathways have no specific role for this mesh, which is often presumed to function primarily as a scaffold that determines cell mechanics but not information flow. We combined analytical tools with several recently established large-scale protein-protein interaction maps for Saccharomyces cerevisiae to quantitatively address the role of the cytoskeleton in intracellular signaling. The results demonstrate that the network of signaling proteins is intimately linked to the cytoskeleton, suggesting that this interconnected filamentous structure plays a crucial and distinct functional role in signal transduction.

Cytoskeleton↗

PubMed2004

Engineering biological structures of prescribed shape using self-assembling multicellular systems.

Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures. Here we show, both experimentally and by using computer simulations, how tissue liquidity can be used to build tissue constructs of prescribed geometry in vitro. Spherical aggregates containing many thousands of cells, which form because of tissue liquidity, were implanted contiguously into biocompatible hydrogels in circular geometry. Depending on the properties of the gel, upon incubation, the aggregates either fused into a toroidal 3D structure or their constituent cells dispersed into the surrounding matrix. The model simulations, which reproduced the experimentally observed shapes, indicate that the control parameter of structure evolution is the aggregate-gel interfacial tension. The model-based analysis also revealed that the observed toroidal structure represents a metastable state of the cellular system, whose lifetime depends on the magnitude of cell-cell and cell-matrix interactions. Thus, these constructs can be made long-lived. We suggest that spherical aggregates composed of organ-specific cells may be used as "bio-ink" in the evolving technology of organ printing.

Animals↗

PubMed2004

Organ printing: fiction or science.

Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops. According to Steinberg's differential adhesion hypothesis (DAH), this may be understood by assuming that cells are motile and tissues made of such cells possess an effective surface tension. Here we show that based on these properties three-dimensional cellular structures of prescribed shape can be constructed by a novel method: cell aggregate printing. Spherical aggregates of similar size made of cells with known adhesive properties were prepared. Aggregates were embedded into biocompatible gels. When the cellular and gel properties, as well as the symmetry of the initial configuration were appropriately adjusted the contiguous aggregates fused into ring-like organ structures. To elucidate the driving force and optimal conditions for this pattern formation, Monte Carlo simulations based on a DAH motivated model were performed. The simulations reproduced the experimentally observed cellular arrangements and revealed that the control parameter of pattern evolution is the gel-tissue interfacial tension, an experimentally accessible parameter.

Biocompatible Materials↗

PubMed2003

Assembly of collagen matrices as a phase transition revealed by structural and rheologic studies.

We have studied the structural and viscoelastic properties of assembling networks of the extracellular matrix protein type-I collagen by means of phase contrast microscopy and rotating disk rheometry. The initial stage of the assembly is a nucleation process of collagen monomers associating to randomly distributed branched clusters with extensions of several microns. Eventually a sol-gel transition takes place, which is due to the interconnection of these clusters. We analyzed this transition in terms of percolation theory. The viscoelastic parameters (storage modulus G' and loss modulus G") were measured as a function of time for five different frequencies ranging from omega = 0.2 rad/s to 6.9 rad/s. We found that at the gel point both G' and G" obey a scaling law, with the critical exponent Delta = 0.7 and a critical loss angle being independent of frequency as predicted by percolation theory. Gelation of collagen thus represents a second order phase transition.

Animals↗

PubMed2003

Organ printing: computer-aided jet-based 3D tissue engineering.

Tissue engineering technology promises to solve the organ transplantation crisis. However, assembly of vascularized 3D soft organs remains a big challenge. Organ printing, which we define as computer-aided, jet-based 3D tissue-engineering of living human organs, offers a possible solution. Organ printing involves three sequential steps: pre-processing or development of "blueprints" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation. A cell printer that can print gels, single cells and cell aggregates has been developed. Layer-by-layer sequentially placed and solidified thin layers of a thermo-reversible gel could serve as "printing paper". Combination of an engineering approach with the developmental biology concept of embryonic tissue fluidity enables the creation of a new rapid prototyping 3D organ printing technology, which will dramatically accelerate and optimize tissue and organ assembly.

Artificial Organs↗

PubMed2002

Mechanotransduction through the cytoskeleton.

We constructed a model cytoskeleton to investigate the proposal that this interconnected filamentous structure can act as a mechano- and signal transducer. The model cytoskeleton is composed of rigid rods representing actin filaments, which are connected with springs representing cross-linker molecules. The entire mesh is placed in viscous cytoplasm. The model eukaryotic cell is submitted to either shock wave-like or periodic mechanical perturbations at its membrane. We calculated the efficiency of this network to transmit energy to the nuclear wall as a function of cross-linker stiffness, cytoplasmic viscosity, and external stimulation frequency. We found that the cytoskeleton behaves as a tunable band filter: for given linker molecules, energy transmission peaks in a narrow range of stimulation frequencies. Most of the normal modes of the network are spread over the same frequency range. Outside this range, signals are practically unable to reach their destination. Changing the cellular ratios of linker molecules with different elastic characteristics can control the allowable frequency range and, with it, the efficiency of mechanotransduction.

Cytoskeleton↗