From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility. In new work, reported in ("Force-Controlled Patch Clamp of Beating Cardiac Cells"), researchers merged the patch clamp and atomic force microscope (AFM) techniques, thus equipping the patch-clamp with the sensitive AFM force control. 
This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage. The tool's ability to obtain simultaneous electrophysiological and mechanical information will render it a valuable tool in the field of mechanotransduction. Yet, the enhanced stability and repeatability of the patch clamp protocol sustained by the force feedback are of interest for the entire field of electrophysiology. In addition, the whole process has the potential to be automated, as both the AFM and the pressure controller are fully programmable.
This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage. The tool's ability to obtain simultaneous electrophysiological and mechanical information will render it a valuable tool in the field of mechanotransduction. Yet, the enhanced stability and repeatability of the patch clamp protocol sustained by the force feedback are of interest for the entire field of electrophysiology. In addition, the whole process has the potential to be automated, as both the AFM and the pressure controller are fully programmable.
covers the recent developments, trends and innovations in the application of nanotechnologies in tissue engineering and regenerative medicine. It provides information on methodologies for designing and using biomaterials to regenerate tissue, on novel nano-textured surface features of materials (nano-structured polymers and metals e.g.) as well as on theranostics, immunology and nano-toxicology aspects. In the book also explained are fabrication techniques for production of scaffolds to a series of tissue-specific applications of scaffolds in tissue engineering for specific biomaterials and several types of tissue (such as skin bone, cartilage, vascular, cardiac, bladder and brain tissue). Furthermore, developments in nano drug delivery, gene therapy and cancer nanotechonology are described. The book helps readers to gain a working knowledge about the nanotechnology aspects of tissue engineering and will be of great use to those involved in building specific tissue substitutes in reaching their objective in a more efficient way. It is aimed for R&D and academic scientists, lab engineers, lecturers and PhD students engaged in the fields of tissue engineering or more generally regenerative medicine, nanomedicine, medical devices, nanofabrication, biofabrication, nano- and biomaterials and biomedical engineering. This book
The ultrashort pulses and high intensity of the X-ray laser permit such rapid data collection that an image of the cell is obtained before it disintegrates. X-rays destroy cells, but the ultrashort pulses and high intensity of the X-ray laser permit such rapid data collection that a correct image of the sample is obtained before it disintegrates. This technique, known as ‘diffraction before destruction’, has been shown previously to work with both organic and inorganic samples. The experiment was performed with the X-ray laser of the Linac Coherent Light Source (LCLS) in the Stanford Linear Accelerator Center, California. Two species of cyanobacteria, Cyanobium gracile and Synechococcus elongatus, were used in the study. The almost cylindrical shape of these cells emerges clearly in reconstruction from diffraction data. According to Tomas Ekeberg, a molecular biophysicist at Uppsala University and leader of the experiment, the images could have been better still if it had been possible for the detectors to handle them the data better. ‘To date, we’ve only managed to reconstruct cells with a resolution of 76 nanometres [= millionths of a millimetre], but the data we’ve collected show that we can get down to 4 nanometres. That means we might be able to distinguish individual proteins, which are of that size,’ Ekeberg says. The reason for the lower resolution, Ekeberg points out, is overexposure — exactly what happens when you take photographs in excessively bright light. In future experiments, it will be possible to correct this. ‘We’ll be able to get much higher resolution when we’re able to use a filter to reduce the overexposure,’ adds Gijs van der Schot, a PhD student and principal author of the publication. Up to now, high-resolution depiction has involved freezing cells and giving them a high radiation dose that kills them during the data collection. The cells have also often been coated with a thin layer of metal to improve the contrast. Static images of cells also normally require long exposure times. The research team’s new method can show the structure of living cells, virtually instantaneously. Every image takes only a few femtoseconds (one femtosecond being a millionth billionth of a second). This kind of tool could help scientists gain a better grasp of hitherto unknown details of cell function and behaviour. ‘Processes like cell division and protein folding could be observed in real time. The technique also makes possible future 3D modelling of processes in the cell, which could give us important insights into complicated disease progression,’ Ekeberg explains. The team is now planning to fine-tune the depiction method with further experiments, and hope to achieve images with a considerably higher resolution. ‘There’s a huge difference between images produced by means of this technique and those from traditional optical microscopy of living cells,’ says Janos Hajdu. ‘Few people thought this was feasible.’