Search results

Intro -- Preface -- Rubber, Meet Road -- When Tech Talks, People Act -- Calm Seas in Turbulent Times -- Instilling Hope and Confidence -- Many Medical Cooks Perfecting the Broth -- The Horizon -- Acknowledgments -- About the Book -- Contents -- About the Author -- 1: Premises -- 1.1 Storytelling -- 1.2 The Gauntlet Thrown Down -- 1.3 Spread the Health -- 1.4 Yeah, Yeah…They All Say That -- 1.5 The Resistance -- 1.6 The Times They Are a Changin' -- 1.7 Prioritization -- 1.8 The Plan -- 1.9 The BIG Hurdle -- 1.10 Premium Care -- 1.11 The Target Function -- 1.12 Subsidiary Goals -- 1.13 Second Class? -- 1.14 Presumptions -- 1.15 Can You Spare Some Change? -- 1.16 If It Ain't Broke, Break It -- 1.17 The "X" Factor -- 1.18 History Class -- 1.19 Hiring Is a Concept, Too -- 1.20 Enjoy the Ride -- 1.21 The Paradox -- 1.22 The Proof Is in the Product -- 1.23 Sustainability -- 1.24 Greed -- 1.25 Give It Away, Give It Away, Give It Away Now -- 2: Deconstruction -- 2.1 To Know How Things Might Be, You Have to Know How Things Got to Be the Way They Are -- 2.2 With All Due Diligence -- 2.3 Asking the Right Questions -- 2.4 A Problem Well Stated Is a Problem Half Solved -- 2.5 Tick, Tick, Tick -- 2.6 Are We There Yet? -- 3: Smells Like Team Spirit -- 3.1 Building Teams, Building Trust -- 3.2 What's Your Problem? -- 3.3 Traps -- 3.4 It Takes an Orchestra to Play a Symphony -- 3.5 Do Unto Others -- 3.6 Example #1: You -- 3.7 Open a Window, Would Ya? -- 3.8 No One Can Whistle a Symphony -- 3.9 Wind It Up, Let It Go -- 3.10 Blame and Shame -- 3.11 Readying Your Team for Dragon Slaying -- 4: Management 360 -- 4.1 Architecting a Self-Sustaining Vision -- 4.2 Knowing What Needs to Be Known (and Putting It to Good Use) -- 4.3 The Deputy Question -- 4.4 Lieutenants -- 4.5 Jeopardy.

Abstract
Extracellular vesicles (EVs) transfer bioactive molecules between cells in a process reminiscent of enveloped viruses. EV cargo delivery is thought to occur by protein-mediated and pH-dependent membrane fusion of the EV and the cellular membrane. However, there is a lack of methods to identify the fusion proteins and resolve their mechanism. We developed and benchmarked an in vitro biophysical assay to investigate EV membrane fusion. The assay was standardized by directly comparing EV and viral fusion with liposomes. We show that EVs and retroviruses fuse with liposomes mimicking the membrane composition of the late endosome in a pH- and protein-dependent manner. Moreover, we directly visualize the stages of membrane fusion using cryo-electron tomography. We find that, unlike most retroviruses, EVs remain fusogenic after acidification and reneutralization. These results provide novel insights into the EV cargo delivery mechanism and an experimental approach to identify the EV fusion machinery.