Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice.

Genes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinases, especially of Ret and the FGF receptors. As such, they play distinct and overlapping roles in embryo morphogenesis and are considered to be tumor suppressors in adult life. Genetic experiments in mice have defined in great detail the role of these genes during embryonic development, however their function in adult mice is less clearly established. Here we generate adult-onset, whole body Spry1/2/4 triple knockout mice. Tumor incidence in triple mutant mice is comparable to that of wild type littermates of up to one year of age, indicating that Sprouty loss per se is not sufficient to initiate tumorigenesis. On the other hand, triple knockout mice do not gain weight as they age, show less visceral fat, and have lower plasma glucose levels than wild type littermates, despite showing similar food intake and slightly reduced motor function. They also show alopecia, eyelid inflammation, and mild hyperthyroidism. Finally, triple knockout mice present phosphaturia and hypophosphatemia, suggesting exacerbated signaling downstream of FGF23. In conclusion, triple knockout mice develop a series of endocrine abnormalities but do not show increased tumor incidence.

Designing Polyelectrolyte Microneedles Based on Borylated Poly(ß-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids.

The use of transdermal delivery for nucleic acid administration is an interesting approach to overcoming limitations of systemic administration routes, such as first-pass effects, the painful needle injection, or their poor biodistribution. Thus, the use of a microneedle-based patch could represent a turning point for nucleic acid delivery, thanks to the possibility of self-administration of the actives in a painless and easy procedure. However, the design of transdermal systems with a higher degree of precision release is a clear need that has not been fully resolved. Committed to tackling this challenge, we present here a microneedle patch that involves a smart delivery system supported by the well-established ability of boronic acid to interact with carbohydrates in a pH-dependent manner. This system builds up a multilayer structure over a solid microneedle platform whose surface has been modified to immobilize glucosamine units that are able to interact with an oligopeptide-end terminated poly(ß-aminoester) that presents a 4-carboxy-3-fluorophenylboronic acid (Bor-pBAE). Thus, sequential layers of the Bor-pBAE and plasmid DNA have been assembled, thanks to the ability of the polymer to interact with the nucleic acid at a basic pH and then gradually release the plasmid under two different conditions of pH (the physiological pH = 7.4 and the acidic pH = 5.1). We set up the design and implementation of this first proof of concept while demonstrating microneedles' safety and functionality. Additionally, we have shown the efficacy of the construct to express the encoded genes in model cell lines. In conclusion, we have established the basis to confirm that this generation of borylated poly(ß-aminoesters) holds great promise as a transdermal local nucleic acid delivery system.

Effectiveness and tolerability of givosiran for the management of acute hepatic porphyria: A monocenter real-life evaluation.

Acute hepatic porphyrias (AHPs) are a family of rare, autosomal, dominantly inherited conditions characterized by abnormalities in the production of heme. Advances in molecular engineering have provided new therapeutic possibilities for modifying the heme synthetic pathway in patients with porphyria. In particular, the RNA interference therapeutic givosiran was approved for the treatment of adults and adolescents with AHP aged >12 years based on the positive results of the phase III trial ENVISION. Despite the extended characterization of the activity of givosiran in clinical trials, reports on the long-term effects and effectiveness of the treatment in clinical practice are still scant. To fill this gap, this case series describes a monocentric Italian cohort of AHP patients treated with givosiran. Overall, our real-life experience supports the clinical evidence that long-term treatment with givosiran is well tolerated and able to provide sustained and continuous benefit to patients with acute intermittent porphyria, as reflected by the reduction in the frequency of attacks. In our series, givosiran treatment was also associated with improvement in assessments of quality of life, pain and fatigue.

Effect of an Alliaceae Encapsulated Extract on Growth Performance, Gut Health, and Intestinal Microbiota in Broiler Chickens Challenged with Eimeria spp.

This study analyzed the effects of an Alliaceae encapsulated extract (AE-e) on daily gain (ADG), feed intake (ADFI), feed conversion ratio (FCR), oocysts per gram of feces (OPG), intestinal lesion (LS), and microbiota composition in broilers challenged with Eimeria spp. A total of 4800 one day Cobb-500 were allotted into 10 treatment groups with 12 replicates of 40 birds in a 2 × 4 + 2 factorial arrangement. The first factor was non-challenged (NC) or challenged (C), the second was four levels of AE-e added in the basal diet, 0 (AE0), 250 (AE250), 500 (AE500), and 750 mg·kg-1 (AE750), plus two ionophore controls, non-challenged (NC-Ion) and challenged (C-Ion). No interactions were observed between factors (NC0, NC250, NC500, NC750, C0, C250, C500, and C750), while C-Ion improved FCR at 21 d. The challenge affected negatively ADG and FCR and promoted enteropathogens in cecum. AE750 improved FCR in the finisher and cumulative phases, while C-Ion had fewer total OPG than C0 and C250. Likewise, at 21d, C250, C500, and C-Ion had fewer LS than C0, while at 28 d, C750 showed lower than C-Ion. In the cecum microbiota, C500 had more Ruminococcus, Firmicutes b, and Intestinimonas than C-Ion. In summary, AE-e showed beneficial results in broilers infected with Eimeria spp.

Biosynthesis of Copper Nanoparticles with Medicinal Plants Extracts: From Extraction Methods to Applications.

Copper nanoparticles (CuNPs) can be synthesized by green methods using plant extracts. These methods are more environmentally friendly and offer improved properties of the synthesized NPs in terms of biocompatibility and functional capabilities. Traditional medicine has a rich history of utilization of herbs for millennia, offering a viable alternative or complementary option to conventional pharmacological medications. Plants of traditional herbal use or those with medicinal properties are candidates to be used to obtain NPs due to their high and complex content of biocompounds with different redox capacities that provide a dynamic reaction environment for NP synthesis. Other synthesis conditions, such as salt precursor concentration, temperature, time synthesis, and pH, have a significant effect on the characteristics of the NPs. This paper will review the properties of some compounds from medicinal plants, plant extract obtention methods alternatives, characteristics of plant extracts, and how they relate to the NP synthesis process. Additionally, the document includes diverse applications associated with CuNPs, starting from antibacterial properties to potential applications in metabolic disease treatment, vegetable tissue culture, therapy, and cardioprotective effect, among others.

Current Trends of Bacterial and Fungal Optoproteins for Novel Optical Applications.

Photoproteins, luminescent proteins or optoproteins are a kind of light-response protein responsible for the conversion of light into biochemical energy that is used by some bacteria or fungi to regulate specific biological processes. Within these specific proteins, there are groups such as the photoreceptors that respond to a given light wavelength and generate reactions susceptible to being used for the development of high-novel applications, such as the optocontrol of metabolic pathways. Photoswitchable proteins play important roles during the development of new materials due to their capacity to change their conformational structure by providing/eliminating a specific light stimulus. Additionally, there are bioluminescent proteins that produce light during a heatless chemical reaction and are useful to be employed as biomarkers in several fields such as imaging, cell biology, disease tracking and pollutant detection. The classification of these optoproteins from bacteria and fungi as photoreceptors or photoresponse elements according to the excitation-emission spectrum (UV-Vis-IR), as well as their potential use in novel applications, is addressed in this article by providing a structured scheme for this broad area of knowledge.

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part I: non-small cell lung cancer and breast cancer

Oligometastatic disease (OMD) defines a cancer status that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While diagnostic imaging tools have considerably improved in recent years, unidentified micrometastases can still evade current detection techniques, allowing the disease to progress. The various OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of early disease control. In view of increasing OMD detection rates in current real-world clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies might translate into promising treatment options. This expert review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of non-small cell lung cancer and breast cancer (Part I), and prostate cancer and colorectal cancer (Part II), aiming to offer specialists a pragmatic framework to help improve patient management (AU)

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part II: prostate cancer and colorectal cancer

Oligometastatic disease (OMD) defines a status of cancer that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While imaging diagnostic tools have considerably improved in recent years, unidentified micrometastases can still escape from current detection techniques allowing disease to progress. The variety of OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of an early disease control. Based on increasing detection rates of OMD in the current real clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies may translate into promising treatment options. This experts’ review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of Non-Small Cell Lung Cancer and Breast Cancer (Part I), and Prostate Cancer and Colorectal Cancer (Part II), aiming to offer specialists a pragmatic framework that might contribute to the improved management of patients (AU)

The Effect of Encapsulated Propyl Propane Thiosulfonate (PTSO) on Apparent Ileal Digestibility and Productive Performance in Broiler Chickens.

This study analyzed the effects of different dietary doses of encapsulated propyl propane thiosulfonate (Pe-PTSO) on the apparent ileal digestibility (AID) of nutrients and productive performance in broilers. A total of 100 one-day-old Cobb 500 were housed in battery cages for 20 days. At 10 days of age, the birds were assigned to one of five diets: negative control (P0), 250 mg/kg of Pe-PTSO (P250), 500 mg/kg of Pe-PTSO (P500), 750 mg/kg of Pe-PTSO (P750), and positive control, nicarbazin-narasin (ION). Titanium dioxide was the external marker, which was added to the diets from day 17 to 20. In the birds fed the P250 diet, there was a significant difference (p ≤ 0.05) in the AID values for amino acids and energy compared to those that consumed the P0 diet. Furthermore, the P250 diet significantly increased (p ≤ 0.05) the average daily weight gain compared to the P0 diet. No significant differences were observed between treatments in average daily feed intake and feed conversion ratio. In summary, the inclusion of 250 mg of encapsulated PTSO per kg in broiler chickens diet improved the digestibility of amino acids and energy, as well as weight gain.

Unravelling the role of individual components in pBAE/polynucleotide polyplexes in the synthesis of tailored carriers for specific applications: on the road to rational formulations.

Oligopeptide end-modified poly(ß-amino ester)s (OM-pBAEs) offer a means for the effective implementation of gene therapeutics in the near future. A fine-tuning of OM-pBAEs to meet application requirements is achieved by the proportional balance of oligopeptides used and provide gene carriers with high transfection efficacy, low toxicity, precise targeting, biocompatibility, and biodegradability. Understanding the influence and conformation of each building block at molecular and biological levels is therefore pivotal for further development and improvement of these gene carriers. Herein, we unmask the role of individual OM-pBAE components and their conformation in OM-pBAE/polynucleotide nanoparticles using a combination of fluorescence resonance energy transfer, enhanced darkfield spectral microscopy, atomic force microscopy, and microscale thermophoresis. We found that modifying the pBAE backbone with three end-terminal amino acids produces unique mechanical and physical properties for each combination. Higher adhesion properties are seen with arginine and lysine-based hybrid nanoparticles, while histidine provides an advantage in terms of construct stability. Our results shed light on the high potential of OM-pBAEs as gene delivery vehicles and provide insights into the influence of the nature of surface charges and the chemical nature of the pBAE modifications on their paths towards endocytosis, endosomal escape, and transfection.

Effect of surface functionalization and loading on the mechanical properties of soft polymeric nanoparticles prepared by nano-emulsion templating.

Drug and gene delivery systems based on polymeric nanoparticles offer a greater efficacy and a reduced toxicity compared to traditional formulations. Recent studies have evidenced that their internalization, biodistribution and efficacy can be affected, among other factors, by their mechanical properties. Here, we analyze by means of Atomic Force Microscopy force spectroscopy how composition, surface functionalization and loading affect the mechanics of nanoparticles. For this purpose, nanoparticles made of Poly(lactic-co-glycolic) (PLGA) and Ethyl cellulose (EC) with different functionalizations and loading were prepared by nano-emulsion templating using the Phase Inversion Composition method (PIC) to form the nano-emulsions. A multiparametric nanomechanical study involving the determination of the Young's modulus, maximum deformation and breakthrough force was carried out. The obtained results showed that composition, surface functionalization and loading affect the nanomechanical properties in a different way, thus requiring, in general, to consider the overall mechanical properties after the addition of a functionalization or loading. A graphical representation method has been proposed enabling to easily identify mechanically equivalent formulations, which is expected to be useful in the development of soft polymeric nanoparticles for pre-clinical and clinical use.

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part II: prostate cancer and colorectal cancer.

Oligometastatic disease (OMD) defines a status of cancer that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While imaging diagnostic tools have considerably improved in recent years, unidentified micrometastases can still escape from current detection techniques allowing disease to progress. The variety of OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of an early disease control. Based on increasing detection rates of OMD in the current real clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies may translate into promising treatment options. This experts' review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of Non-Small Cell Lung Cancer and Breast Cancer (Part I), and Prostate Cancer and Colorectal Cancer (Part II), aiming to offer specialists a pragmatic framework that might contribute to the improved management of patients.

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part I: non-small cell lung cancer and breast cancer.

Oligometastatic disease (OMD) defines a cancer status that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While diagnostic imaging tools have considerably improved in recent years, unidentified micrometastases can still evade current detection techniques, allowing the disease to progress. The various OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of early disease control. In view of increasing OMD detection rates in current real-world clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies might translate into promising treatment options. This expert review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of non-small cell lung cancer and breast cancer (Part I), and prostate cancer and colorectal cancer (Part II), aiming to offer specialists a pragmatic framework to help improve patient management.

Biomolecule-Based Optical Metamaterials: Design and Applications.

Metamaterials are broadly defined as artificial, electromagnetically homogeneous structures that exhibit unusual physical properties that are not present in nature. They possess extraordinary capabilities to bend electromagnetic waves. Their size, shape and composition can be engineered to modify their characteristics, such as iridescence, color shift, absorbance at different wavelengths, etc., and harness them as biosensors. Metamaterial construction from biological sources such as carbohydrates, proteins and nucleic acids represents a low-cost alternative, rendering high quantities and yields. In addition, the malleability of these biomaterials makes it possible to fabricate an endless number of structured materials such as composited nanoparticles, biofilms, nanofibers, quantum dots, and many others, with very specific, invaluable and tremendously useful optical characteristics. The intrinsic characteristics observed in biomaterials make them suitable for biomedical applications. This review addresses the optical characteristics of metamaterials obtained from the major macromolecules found in nature: carbohydrates, proteins and DNA, highlighting their biosensor field use, and pointing out their physical properties and production paths.

SARS-CoV-2 indoor environment contamination with epidemiological and experimental investigations.

SARS-CoV-2 has been detected both in air and on surfaces, but questions remain about the patient-specific and environmental factors affecting virus transmission. Additionally, more detailed information on viral sampling of the air is needed. This prospective cohort study (N = 56) presents results from 258 air and 252 surface samples from the surroundings of 23 hospitalized and eight home-treated COVID-19 index patients between July 2020 and March 2021 and compares the results between the measured environments and patient factors. Additionally, epidemiological and experimental investigations were performed. The proportions of qRT-PCR-positive air (10.7% hospital/17.6% homes) and surface samples (8.8%/12.9%) showed statistical similarity in hospital and homes. Significant SARS-CoV-2 air contamination was observed in a large (655.25 m3 ) mechanically ventilated (1.67 air changes per hour, 32.4-421 L/s/patient) patient hall even with only two patients present. All positive air samples were obtained in the absence of aerosol-generating procedures. In four cases, positive environmental samples were detected after the patients had developed a neutralizing IgG response. SARS-CoV-2 RNA was detected in the following particle sizes: 0.65-4.7 µm, 7.0-12.0 µm, >10 µm, and <100 µm. Appropriate infection control against airborne and surface transmission routes is needed in both environments, even after antibody production has begun.

Pineapple stem-derived bromelain based priming improves pepper seed protein reserve mobilization, germination, emergence and plant growth.

Pepper seeds are slow to germinate and emergence is often non-uniform and incomplete, reducing gains from this cash crop. This study investigated the effects of pineapple stem- derived protease (stem bromelain) based priming on pepper seed germination in relation to reserve mobilization (specifically, proteins and amino acids), germination, emergence and plant growth. These parameters were compared across two controls, (1) unsoaked seeds and (2) seeds soaked in deionized water, and seeds soaked in pineapple stem bromelain crude extract (treatment). Seeds were soaked in bromelain crude extract possessing a proteolytic activity of 6.25 tU or deionized water (first control) for 3 h at 35 °C. Light microscopy revealed an abundance of protein bodies in the endosperm of the seeds prior to imbibition. When observed for a period of 96 h, these bodies were progressively degraded, with the rate of this degradation being fastest in bromelain-treated seeds. Quantitative analysis of protein levels confirmed this observation: 17.2 mg proteins/g FW at 120 h after priming in bromelain-treated seeds compared with 22.1 mg/g FW in controls (average). The bromelain treatment also increased levels of free amino acids from 3.9 mg/g FW in the controls to 4.6 mg/g FW after 120 h of imbibition. Germination and emergence percentages were initially higher in bromelain-treated seeds: 92.0% germination in bromelain-treated seeds vs. ~ 52.2% in the controls at 18 d; 100% emergence in protease-treated seeds vs. ~ 72.2% in the controls at 18 d. However, these parameters were comparable across the treatment and the controls at 28 d. Importantly, plant fresh and dry weights were significantly higher when seeds were primed with bromelain. The results suggest the use of bromelain extracts for priming pepper seeds based on their proteolytic activity, since germination is dependent on the availability of crude protein and essential amino acids. The benefits of bromelain seed priming appear to translate into improved seedling growth as well.

Dielectric properties and lamellarity of single liposomes measured by in-liquid scanning dielectric microscopy.

Liposomes are widely used as drug delivery carriers and as cell model systems. Here, we measure the dielectric properties of individual liposomes adsorbed on a metal electrode by in-liquid scanning dielectric microscopy in force detection mode. From the measurements the lamellarity of the liposomes, the separation between the lamellae and the specific capacitance of the lipid bilayer can be obtained. As application we considered the case of non-extruded DOPC liposomes with radii in the range ~ 100-800 nm. Uni-, bi- and tri-lamellar liposomes have been identified, with the largest population corresponding to bi-lamellar liposomes. The interlamellar separation in the bi-lamellar liposomes is found to be below ~ 10 nm in most instances. The specific capacitance of the DOPC lipid bilayer is found to be ~ 0.75 µF/cm2 in excellent agreement with the value determined on solid supported planar lipid bilayers. The lamellarity of the DOPC liposomes shows the usual correlation with the liposome's size. No correlation is found, instead, with the shape of the adsorbed liposomes. The proposed approach offers a powerful label-free and non-invasive method to determine the lamellarity and dielectric properties of single liposomes.

IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection.

The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgA-DIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN.

Functionalized PLGA nanoparticles prepared by nano-emulsion templating interact selectively with proteins involved in the transport through the blood-brain barrier.

During the last few decades, extensive efforts has been made to design nanocarriers to transport drugs into the central nervous system (CNS). However, its efficacy is limited due to the presence of the Blood-Brain Barrier (BBB) which greatly reduces drug penetration making Drug Delivery Systems (DDS) necessary. Polymeric nanoparticles (NPs) have been reported to be appropriate for this purpose and in particular, poly(lactic-co-glycolic acid) (PLGA) has been used for its ability to entrap small molecule drugs with great efficiency and the ease with which it functionalizes NPs. Despite the fact that their synthetic identity has been studied in depth, the biological identity of such manufactured polymers still remains unknown as does their biodistribution and in vivo fate. This biological identity is a result of their interaction with blood proteins, the so-called "protein corona" which tends to alter the behavior of polymeric nanoparticles in the body. The aim of the present research is to identify the proteins bounded to polymeric nanoparticles designed to selectively interact with the BBB. For this purpose, four different PLGA NPs were prepared and analyzed: (i) "PLGA@Drug," in which a model drug was encapsulated in its core; (ii) "8D3-PLGA" NPs where the PLGA surface was functionalized with a monoclonal anti-transferrin receptor antibody (8D3 mAb) in order to specifically target the BBB; (iii) "8D3-PLGA@Drug" in which the PLGA@Drug surface was functionalized using the same antibody described above and (iv) bare PLGA NPs which were used as a control. Once the anticipated protein corona NPs were obtained, proteins decorating both bare and functionalized PLGA NPs were isolated and analyzed. Apart from the indistinct interaction with PLGA NPs with the most abundant serum proteins, specific proteins could also be identified in the case of functionalized PLGA NPs. These findings may provide valuable insight into designing novel vehicles based on PLGA NPs for crossing the BBB.

Artificial Cell Membranes Interfaced with Optical Tweezers: A Versatile Microfluidics Platform for Nanomanipulation and Mechanical Characterization.

Cell lipid membranes are the site of vital biological processes, such as motility, trafficking, and sensing, many of which involve mechanical forces. Elucidating the interplay between such bioprocesses and mechanical forces requires the use of tools that apply and measure piconewton-level forces, e.g., optical tweezers. Here, we introduce the combination of optical tweezers with free-standing lipid bilayers, which are fully accessible on both sides of the membrane. In the vicinity of the lipid bilayer, optical trapping would normally be impossible due to optical distortions caused by pockets of the solvent trapped within the membrane. We solve this by drastically reducing the size of these pockets via tuning of the solvent and flow cell material. In the resulting flow cells, lipid nanotubes are straightforwardly pushed or pulled and reach lengths above half a millimeter. Moreover, the controlled pushing of a lipid nanotube with an optically trapped bead provides an accurate and direct measurement of important mechanical properties. In particular, we measure the membrane tension of a free-standing membrane composed of a mixture of dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) to be 4.6 × 10-6 N/m. We demonstrate the potential of the platform for biophysical studies by inserting the cell-penetrating trans-activator of transcription (TAT) peptide in the lipid membrane. The interactions between the TAT peptide and the membrane are found to decrease the value of the membrane tension to 2.1 × 10-6 N/m. This method is also fully compatible with electrophysiological measurements and presents new possibilities for the study of membrane mechanics and the creation of artificial lipid tube networks of great importance in intra- and intercellular communication.